Methods and compositions for the specific inhibition of MYC by double-stranded RNA

ABSTRACT

This invention relates to compounds, compositions, and methods useful for reducing MYC target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

RELATED APPLICATIONS

The present application is the U.S. national phase, pursuant to 35U.S.C. §371, of international application Ser. No. PCT/US2013/059391,filed Sep. 12, 2013, designating the United States and published inEnglish on Mar. 20, 2014 as publication No. WO 2014/043311 A1, whichclaims priority to, and the benefit under 35 U.S.C. §119(e) of thefollowing applications: U.S. provisional patent application No.61/701,136, entitled “Methods and Compositions for the SpecificInhibition of MYC by Double-Stranded RNA,” filed Sep. 14, 2012; and U.S.provisional patent application No. 61/786,695 entitled “Methods andCompositions for the Specific Inhibition of MYC by Double-Stranded RNA,”filed Mar. 15, 2013. The entire contents of the aforementioned patentapplications are incorporated herein by this reference.

FIELD OF THE INVENTION

The present invention relates to compounds, compositions, and methodsfor the study, diagnosis, and treatment of traits, diseases andconditions that respond to the modulation of c-Myc gene expressionand/or activity.

BACKGROUND OF THE INVENTION

The c-MYC (MYC) gene is a key molecular regulator of cellular growth anddifferentiation. Myc protein is a transcription factor that activatesexpression of many genes via binding of consensus sequences (EnhancerBox sequences (E-boxes)) and recruitment of histone acetyltransferases(HATs). Myc can also act as a transcriptional repressor. By bindingMiz-1 transcription factor and displacing the p300 co-activator, Mycinhibits expression of Miz-1 target genes. In addition, Myc has a directrole in the control of DNA replication (Dominguez-Sola et al. Nature 448(7152): 445-51).

Various mitogenic signaling pathways, including Wnt, Shh and EGF (viathe MAPK/ERK pathway), have been demonstrated to activate Myc. Myc'srole in modifying the expression of its target genes has been shown tocause numerous biological effects. The first to be discovered was itscapability to drive cell proliferation (upregulates cyclins,downregulates p21), but Myc also plays a very important role inregulating cell growth (upregulates ribosomal RNA and proteins),apoptosis (downregulates Bcl-2), differentiation and stem cellself-renewal. Myc is a strong proto-oncogene and it its upregulation hasbeen described in many types of cancers. Myc overexpression stimulatesgene amplification (Denis et al. Oncogene 6 (8): 1453-7), via amechanism believed to involve DNA over-replication.

At least because of the MYC oncogene's propensity to increase cellproliferation when specifically mutated or overexpressed, MYC is anattractive target for inhibitory oncotherapeutics, including smallmolecule and nucleic acid inhibitors of MYC.

Double-stranded RNA (dsRNA) agents possessing strand lengths of 25 to 35nucleotides have been described as effective inhibitors of target geneexpression in mammalian cells (Rossi et al., U.S. Patent ApplicationNos. 2005/0244858 and US 2005/0277610). dsRNA agents of such length arebelieved to be processed by the Dicer enzyme of the RNA interference(RNAi) pathway, leading such agents to be termed “Dicer substrate siRNA”(“DsiRNA”) agents. Additional modified structures of DsiRNA agents werepreviously described (Rossi et al., U.S. Patent Application No.2007/0265220).

Provided herein are improved nucleic acid agents that target MYC. Inparticular, those targeting MYC have been specifically exemplified.

BRIEF SUMMARY OF THE INVENTION

The present invention is directed to nucleic acid compositions thatreduce expression of MYC. Such compositions contain nucleic acids suchas double stranded RNA (“dsRNA”), and methods for preparing them. Thenucleic acids of the invention are capable of reducing the expression ofa target MYC gene in a cell, either in vitro or in a mammalian subject.

In one aspect, the invention provides an isolated nucleic acid having anoligonucleotide strand of 15-35 nucleotides in length, where theoligonucleotide strand is sufficiently complementary to a target MYCmRNA sequence of Table 15 along at least 15 nucleotides of theoligonucleotide strand length to reduce MYC target mRNA expression whenthe nucleic acid is introduced into a mammalian cell.

Another aspect of the invention provides an isolated nucleic acid havingan oligonucleotide strand of 19-35 nucleotides in length, where theoligonucleotide strand is sufficiently complementary to a target MYCmRNA sequence of Table 14 along at least 19 nucleotides of theoligonucleotide strand length to reduce MYC target mRNA expression whenthe nucleic acid is introduced into a mammalian cell.

An additional aspect of the invention provides an isolated doublestranded nucleic acid (dsNA) having first and second nucleic acidstrands possessing RNA, where the first strand is 15-35 nucleotides inlength and the second strand of the dsNA is 19-35 nucleotides in length,where the second oligonucleotide strand is sufficiently complementary toa target MYC mRNA sequence of Table 15 along at least 15 nucleotides ofthe second oligonucleotide strand length to reduce MYC target mRNAexpression when the double stranded nucleic acid is introduced into amammalian cell.

A further aspect of the invention provides an isolated double strandednucleic acid (dsNA) having first and second nucleic acid strands, wherethe first strand is 15-35 nucleotides in length and the second strand ofthe dsNA is 19-35 nucleotides in length, where the secondoligonucleotide strand is sufficiently complementary to a target MYCmRNA sequence of Table 14 along at least 19 nucleotides of the secondoligonucleotide strand length to reduce MYC target mRNA expression whenthe double stranded nucleic acid is introduced into a mammalian cell.

Another aspect of the invention provides an isolated double strandednucleic acid (dsNA) having first and second nucleic acid strands, wherethe first strand is 15-35 nucleotides in length and the second strand ofthe dsNA is 19-35 nucleotides in length, where the secondoligonucleotide strand is sufficiently complementary to a target MYCmRNA sequence of Table 13 along at least 19 nucleotides of the secondoligonucleotide strand length to reduce MYC target mRNA expression, andwherein, starting from the 5′ end of the MYC mRNA sequence of Table 13(position 1), mammalian Ago2 cleaves the mRNA at a site betweenpositions 9 and 10 of the sequence, when the double stranded nucleicacid is introduced into a mammalian cell.

An additional aspect of the invention provides an isolated dsNA moleculeformed by: (a) a sense region and an antisense region, where the senseregion and the antisense region together form a duplex region of 25-35base pairs and the antisense region contains a sequence that is thecomplement of a sequence of Table 12; and (b) from zero to two 3′overhang regions, where each overhang region is six or fewer nucleotidesin length.

A further aspect of the invention provides an isolated dsNA moleculeformed by: (a) a sense region and an antisense region, where the senseregion and the antisense region together form a duplex region of 25-35base pairs and the antisense region contains a sequence that is thecomplement of a sequence of Table 12; and (b) from zero to two 3′overhang regions, wherein each overhang region is six or fewernucleotides in length, and where, starting from the 5′ end of the MYCmRNA sequence of Table 11 (position 1), mammalian Ago2 cleaves the mRNAat a site between positions 9 and 10 of the sequence, when the doublestranded nucleic acid is introduced into a mammalian cell.

Another aspect of the invention provides an isolated double strandednucleic acid (dsNA) having first and second nucleic acid strands and aduplex region of at least 25 base pairs, where the first strand is 25-34nucleotides in length and the second strand of the dsNA is 26-35nucleotides in length and possesses 1-5 single-stranded nucleotides atits 3′ terminus, where the second oligonucleotide strand is sufficientlycomplementary to a target MYC mRNA sequence of Table 11 along at least19 nucleotides of the second oligonucleotide strand length to reduce MYCtarget gene expression when the double stranded nucleic acid isintroduced into a mammalian cell.

In another aspect, the invention provides an isolated double strandednucleic acid (dsNA) having first and second nucleic acid strands and aduplex region of at least 25 base pairs, where the first strand is 25-34nucleotides in length and the second strand of the dsNA is 26-35nucleotides in length and possesses 1-5 single-stranded nucleotides atits 3′ terminus, wherein the 3′ terminus of the first oligonucleotidestrand and the 5′ terminus of the second oligonucleotide strand form ablunt end, and the second oligonucleotide strand is sufficientlycomplementary to a target MYC sequence of SEQ ID NOs: 1309-1635 and1963-3270 along at least 19 nucleotides of the second oligonucleotidestrand length to reduce MYC mRNA expression when the double strandednucleic acid is introduced into a mammalian cell.

In one embodiment, the isolated dsNA has a duplex region of at least 25base pairs, 19-21 base pairs or 21-25 base pairs. In another embodiment,the second oligonucleotide strand possesses 1-5 single-strandednucleotides at its 3′ terminus. In a further embodiment, the firststrand is 25-35 nucleotides in length. In certain embodiments, theinvention also provides for an isolated dsNA where the first strand is26-35 nucleotides in length, 27-35 nucleotides in length, 28-35nucleotides in length, 29-35 nucleotides in length, 30-35 nucleotides inlength, 31-35 nucleotides in length, 33-35 nucleotides in length, 34-35nucleotides in length, 17-35 nucleotides in length, 19-35 nucleotides inlength, 21-35 nucleotides in length, 23-35 nucleotides in length, 17-33nucleotides in length, 17-31 nucleotides in length, 17-29 nucleotides inlength, 17-27 nucleotides in length, 21-35 nucleotides in length or19-33 nucleotides in length.

In one embodiment, the second strand is 25-35 nucleotides in length. Incertain embodiments, the invention also provides for an isolated dsNAwhere the second strand is 26-35 nucleotides in length, 27-35nucleotides in length, 28-35 nucleotides in length, 29-35 nucleotides inlength, 30-35 nucleotides in length, 31-35 nucleotides in length, 33-35nucleotides in length, 34-35 nucleotides in length, 21-35 nucleotides inlength, 23-35 nucleotides in length, 25-35 nucleotides in length, 27-35nucleotides in length, 19-33 nucleotides in length, 19-31 nucleotides inlength, 19-29 nucleotides in length, 19-27 nucleotides in length or19-25 nucleotides in length.

In another embodiment, the second oligonucleotide strand iscomplementary to a target MYC cDNA sequence of GenBank Accession Nos.NM_002467.4 and NM_010849.4 along at most 27 nucleotides of the secondoligonucleotide strand length.

In one embodiment, the dsNA includes a modified nucleotide. Optionally,the modified nucleotide residue is 2′-O-methyl, 2′-methoxyethoxy,2′-fluoro, 2′-allyl, 2′-O-[2-(methylamino)-2-oxoethyl], 4′-thio,4′-CH2-O-2′-bridge, 4′-(CH2)2-O-2′-bridge, 2′-LNA, 2′-amino or2′-O-(N-methlycarbamate).

In certain embodiments, starting from the first nucleotide (position 1)at the 3′ terminus of the first oligonucleotide strand, position 1, 2and/or 3 is substituted with a modified nucleotide. Optionally, themodified nucleotide residue of the 3′ terminus of the first strand is adeoxyribonucleotide, an acyclonucleotide or a fluorescent molecule. Incertain embodiments, position 1 of the 3′ terminus of the firstoligonucleotide strand is a deoxyribonucleotide

In one embodiment, the 3′ terminus of the first strand and the 5′terminus of the second strand form a blunt end.

In another embodiment, the first strand is 25 nucleotides in length andthe second strand is 27 nucleotides in length. In a further embodiment,starting from the 5′ end of a MYC mRNA sequence of Table 10 (position1), mammalian Ago2 cleaves the mRNA at a site between positions 9 and 10of the sequence, thereby reducing MYC target mRNA expression when thedouble stranded nucleic acid is introduced into a mammalian cell. Incertain embodiments, starting from the 5′ end of a MYC mRNA sequence ofSEQ ID NOs: 1309-1635 or 1963-2289, mammalian Ago2 cleaves the mRNA at asite between positions 9 and 10 of the mRNA sequence, thereby reducingMYC target mRNA expression when the double stranded nucleic acid isintroduced into a mammalian cell.

In one embodiment, the second strand includes a sequence of SEQ ID NOs:328-654.

In another embodiment, the first strand includes a sequence of SEQ IDNOs: 1-327, 982-1308 and 1636-1962.

In certain embodiments, a dsNA of the invention includes a pair of firststrand/second strand sequences of Table 2.

In some embodiments, each of the first and the second strands has alength which is at least 26 nucleotides. The invention also provides foran isolated dsNA where each of the first and the second strands has alength which is at least 27 nucleotides, at least 28 nucleotides, atleast 29 nucleotides, at least 30 nucleotides, at least 31 nucleotides,at least 32 nucleotides, at least 33 nucleotides, at least 34nucleotides or at least 35 nucleotides.

In certain embodiments, the nucleotides of the 1-5 single-strandednucleotides of the 3′ terminus of the second strand include a modifiednucleotide. Optionally, the modified nucleotide of the 1-5single-stranded nucleotides of the 3′ terminus of the second strand is a2′-O-methyl ribonucleotide. In some embodiments, all nucleotides of the1-5 single-stranded nucleotides of the 3′ terminus of the second strandare modified nucleotides. In one embodiment, the 1-5 single-strandednucleotides of the 3′ terminus of the second strand are 1-3 or,optionally, 1-2 nucleotides in length. In certain embodiments, the 1-5single-stranded nucleotides of the 3′ terminus of the second strand istwo nucleotides in length and includes a 2′-O-methyl modifiedribonucleotide.

In one embodiment, the second oligonucleotide strand possesses amodification pattern of AS-M1 to AS-M46 and AS-M1* to AS-M46*. Inanother embodiment, the first oligonucleotide strand possesses amodification pattern of SM1 to SM22.

In another embodiment, each of the first and the second strands has alength which is at least 26 and at most 30 nucleotides. The inventionalso provides for an isolated dsNA, wherein either or each of the firstand the second strands has a length which is at least 27 and at most 30nucleotides, at least 28 and at most 30 nucleotides and at least 29 orat most 30 nucleotides.

In certain embodiments, the dsNA is cleaved endogenously in a cell byDicer.

In some embodiments, the amount of the isolated nucleic acid sufficientto reduce expression of the target gene is 1 nanomolar or less, 200picomolar or less, 100 picomolar or less, 50 picomolar or less, 20picomolar or less, 10 picomolar or less, 5 picomolar or less, 2,picomolar or less or 1 picomolar or less in the environment of the cell.

In one embodiment, an isolated dsNA of the invention possesses greaterpotency than an isolated 21mer siRNA directed to the identical at least19 nucleotides of the target MYC mRNA in reducing target MYC mRNAexpression when assayed in vitro in a mammalian cell at an effectiveconcentration in the environment of a cell of 1 nanomolar or less.

In another embodiment, an isolated dsNA of the invention is sufficientlycomplementary to the target MYC mRNA sequence to reduce MYC target mRNAexpression by an amount (expressed by %) of at least 10%, at least 50%,at least 80-90%, at least 95%, at least 98%, or at least 99% when thedouble stranded nucleic acid is introduced into a mammalian cell. Inrelated embodiments, the invention provides for an isolated dsNA that issufficienctly complementar to a target MYC mRNA sequence along at least15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more nucleotides of thesecond oligonucleotide strand length to reduce MYC target mRNAexpression when the dsNA is introduced into a mammalian cell.

In one embodiment, the first and second strands of a dsNA of theinvention are joined by a chemical linker. Optionally, the 3′ terminusof the first strand and the 5′ terminus of the second strand are joinedby a chemical linker.

In certain embodiments, a nucleotide of the second or first strand issubstituted with a modified nucleotide that directs the orientation ofDicer cleavage.

In some embodiments, an isolated nucleic acid of the invention possessesa modified nucleotide that is a deoxyribonucleotide, adideoxyribonucleotide, an acyclonucleotide, a 3′-deoxyadenosine(cordycepin), a 3′-azido-3′-deoxythymidine (AZT), a 2′,3′-dideoxyinosine(ddI), a 2′,3′-dideoxy-3′-thiacytidine (3TC), a2′,3′-didehydro-2′,3′-dideoxythymidine (d4T), a monophosphate nucleotideof 3′-azido-3′-deoxythymidine (AZT), a 2′,3′-dideoxy-3′-thiacytidine(3TC) and a monophosphate nucleotide of2′,3′-didehydro-2′,3′-dideoxythymidine (d4T), a 4-thiouracil, a5-bromouracil, a 5-iodouracil, a 5-(3-aminoallyl)-uracil, a 2′-O-alkylribonucleotide, a 2′-O-methyl ribonucleotide, a 2′-amino ribonucleotide,a 2′-fluoro ribonucleotide, or a locked nucleic acid.

In one embodiment, a dsNA of the invention possesses a phosphatebackbone modification that is a phosphonate, a phosphorothioate or aphosphotriester.

Optionally, a dsNA of the invention possesses a modification that is amorpholino nucleic acid or a peptide nucleic acid (PNA).

Another aspect of the invention provides a method for reducingexpression of a target MYC gene in a mammalian cell involving contactinga mammalian cell in vitro with an isolated dsNA of the invention in anamount sufficient to reduce expression of a target MYC mRNA in the cell.

In one embodiment, MYC mRNA levels are reduced by an amount (expressedby %) of at least 90% at least 8 days after the cell is contacted withthe dsNA. In another embodiment, MYC mRNA levels are reduced by anamount (expressed by %) of at least 70% at least 10 days after the cellis contacted with the dsNA.

A further aspect of the invention provides a method for reducingexpression of a target MYC mRNA in a mammal involving administering anisolated nucleic acid of the invention in an amount sufficient to reduceexpression of a target MYC mRNA in the mammal.

Another aspect of the invention provides a method for reducing tumorburden in a mammal involving administering an isolated nucleic acid ofthe invention to a mammal in an amount sufficient to reduce tumor burdenin the mammal.

In one embodiment, the tumor is a hepatocellular carcinoma. In anotherembodiment, the tumor burden is reduced by 50-80%, as compared to asuitable control.

In certain embodiments, the isolated nucleic acid is formulated in alipid nanoparticle (LNP).

In some embodiments, the isolated nucleic acid is administered at adosage of 1 microgram to 5 milligrams per kilogram of the mammal perday, 100 micrograms to 0.5 milligrams per kilogram, 0.001 to 0.25milligrams per kilogram, 0.01 to 20 micrograms per kilogram, 0.01 to 10micrograms per kilogram, 0.10 to 5 micrograms per kilogram, or 0.1 to2.5 micrograms per kilogram.

In certain embodiments, the isolated nucleic acid of the inventionpossesses greater potency than isolated 21mer siRNAs directed to theidentical at least 19 nucleotides of the target MYC mRNA in reducingtarget MYC mRNA expression when assayed in vitro in a mammalian cell atan effective concentration in the environment of a cell of 1 nanomolaror less.

In one embodiment, MYC mRNA levels are reduced in a tissue of the mammalby an amount (expressed by %) of at least 70% at least 3 days after theisolated dsNA is administered to the mammal. Optionally, the tissue isliver tissue.

In some embodiments, the administering step involves intravenousinjection, intramuscular injection, intraperitoneal injection, infusion,subcutaneous injection, transdermal, aerosol, rectal, vaginal, topical,oral or inhaled delivery.

A further aspect of the invention provides a method for selectivelyinhibiting the growth of a cell that involves contacting a cell with anamount of an isolated nucleic acid of the invention sufficient toinhibit the growth of the cell.

In one embodiment, the cell is a tumor cell of a subject. Optionally,the cell is a tumor cell in vitro. In a related embodiment, the cell isa human cell.

Another aspect of the invention provides a formulation that includes theisolated nucleic acid of the invention, where the nucleic acid ispresent in an amount effective to reduce target MYC mRNA levels when thenucleic acid is introduced into a mammalian cell in vitro by an amount(expressed by %) of at least 10%, at least 50% or at least 80-90%.

In one embodiment, the effective amount is 1 nanomolar or less, 200picomolar or less, 100 picomolar or less, 50 picomolar or less, 20picomolar or less, 10 picomolar or less, 5 picomolar or less, 2,picomolar or less or 1 picomolar or less in the environment of the cell.

An additional aspect of the invention provides a formulation containingthe isolated dsNA of the invention, where the dsNA is present in anamount effective to reduce target MYC mRNA levels when the dsNA isintroduced into a cell of a mammalian subject by an amount (expressed by%) of the group consisting of at least 10%, at least 50% and at least80-90%.

In one embodiment, the effective amount is a dosage of 1 microgram to 5milligrams per kilogram of the subject per day, 100 micrograms to 0.5milligrams per kilogram, 0.001 to 0.25 milligrams per kilogram, 0.01 to20 micrograms per kilogram, 0.01 to 10 micrograms per kilogram, 0.10 to5 micrograms per kilogram, or 0.1 to 2.5 micrograms per kilogram.

Another aspect of the invention provides a mammalian cell containing anisolated nucleic acid of the invention.

A further aspect of the invention provides a pharmaceutical compositioncontaining the isolated nucleic acid of the invention and apharmaceutically acceptable carrier.

An additional aspect of the invention provides a kit that includes theisolated nucleic acid of the invention and instructions for its use.

In another aspect, the invention provides a method for treating orpreventing a MYC-associated disease or disorder in a subject thatinvolves administering an isolated nucleic acid of the invention and apharmaceutically acceptable carrier to the subject in an amountsufficient to treat or prevent the MYC-associated disease or disorder inthe subject, thereby treating or preventing the MYC-associated diseaseor disorder in the subject.

In one embodiment, the MYC-associated disease or disorder is liver,renal, breast, lung, ovarian, cervical, esophageal, oropharyngeal orpancreatic cancer. Optionally, the MYC-associated disease or disorder ishepatocellular carcinoma.

Another aspect of the invention provides a composition possessing MYCinhibitory activity consisting essentially of an isolated nucleic acidof the invention.

The present invention is also directed to compounds, compositions, andmethods relating to traits, diseases and conditions that respond to themodulation of expression and/or activity of genes involved in MYC geneexpression pathways or other cellular processes that mediate themaintenance or development of such traits, diseases and conditions. Incertain aspects, the invention relates to small nucleic acid moleculesthat are capable of being processed by the Dicer enzyme, such as Dicersubstrate siRNAs (DsiRNAs) capable of mediating RNA interference (RNAi)against MYC gene expression. The anti-MYC dsRNAs of the invention areuseful, for example, in providing compositions for treatment of traits,diseases and conditions that can respond to modulation of MYC in asubject, such as cancer and/or other proliferative diseases, disorders,or conditions. Efficacy, potency, toxicity and other effects of ananti-MYC dsRNA can be examined in one or more animal models ofproliferative disease (exemplary animal models of proliferative diseaseare recited below).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the structures of exemplary DsiRNA agents of the inventiontargeting a site in the MYC RNA referred to herein as the “MYC-953”target site. UPPER case=unmodified RNA, lower case=DNA, Bold=mismatchbase pair nucleotides; arrowheads indicate projected Dicer enzymecleavage sites; dashed line indicates sense strand (top strand)sequences corresponding to the projected Argonaute 2 (Ago2) cleavagesite within the targeted MYC sequence.

FIGS. 2A to 2H present primary screen data showing DsiRNA-mediatedknockdown of human MYC (FIGS. 2A to 2D) and mouse MYC (FIGS. 2E to 2H)in human and mouse cells, respectively. For each DsiRNA tested, threeindependent qPCR amplicons were assayed (in human cells, amplicons“514-620”, “1227-1347” and “1771-1872” were assayed, while in mousecells, amplicons “539-663”, “1339-1428” and “1971-2062” were assayed).

FIGS. 3A to 3H show histograms of human and mouse MYC inhibitoryefficacies observed for indicated DsiRNAs. “P1” indicates phase 1(primary screen), while “P2” indicates phase 2. In phase 1, DsiRNAs weretested at 1 nM in the environment of A549 cells (human cell assays;FIGS. 3A to 3D) or mouse cells (Hepa 1-6 cell assays; FIGS. 3E to 3H).In phase 2, DsiRNAs were tested at 1 nM and at 0.1 nM (duplicate assays)in the environment of A549 cells. Individual bars represent averagehuman (FIGS. 3A to 3D) or mouse (FIGS. 3E to 3H) MYC levels observed intriplicate, with standard errors shown. Human MYC levels were normalizedto HPRT and SFRS9 levels, while mouse MYC levels were normalized to HPRTand Rp123 levels.

FIGS. 4A to 4H present histograms showing efficacy data for 24independent MYC-targeting DsiRNA sequences across four different guide(antisense) strand 2′-O-methyl modification patterns (“M17”, “M35”,“M48” and “M8”, respectively, as shown in FIGS. 4A to 4H, noting thatmodification patterns are recited as passenger strand modificationpattern (here, “M0”, or unmodified)-guide strand modification pattern,e.g., “M0-M17”, “M0-M35”, “M0-M48” or “M0-M8”) in human A549 cells(FIGS. 4A to 4D) and mouse Hepa 1-6 cells (FIGS. 4E to 4H) at 0.1 nM(duplicate assays) and 1 nM.

FIGS. 5A to 5F present histograms showing efficacy data for 19independent MYC-targeting DsiRNA sequences across varying passenger(sense) and guide (antisense) strand 2′-O-methyl modification patterns(modification patterns are recited as passenger strand modificationpattern-guide strand modification pattern) in human A549 cells at 0.1 nM(duplicate assays) and 1 nM, with comparison to phase I (unmodified)levels of inhibition at 1 nM also shown.

FIGS. 6A to 6D show histograms demonstrating efficacy data for sevenindependent MYC-targeting DsiRNA sequences that incorporate mismatcheswith respect to the MYC mRNA target sequence, in human A549 cells at 0.1nM (duplicate assays) and 1 nM, with comparison to phase 4 results(obtained with the native sequence only, which does not include anymismatches) at 1 nM also shown.

FIGS. 7A to 7L present an additional 2′-O-methyl modification screenperformed upon MYC-622, MYC-953 and MYC-1711 duplexes. FIGS. 7A to 7Hshow schematic depictions of duplex modifications used in such assays,while FIGS. 71 and 7J present schematic depctions of individual sensestrand and antisense strand 2′-O-methyl modification patterns,respectively. FIGS. 7K and 7L display histograms showing efficacy datafor these MYC-targeting DsiRNA sequences across the varying passenger(sense) and guide (antisense) strand 2′-O-methyl modification patterns(modification patterns are recited as passenger strand modificationpattern-guide strand modification pattern) in human A549 cells at 0.1 nM(duplicate assays) and 1 nM, with comparison to phase 5 (possessing aM12-M48 modification) levels of inhibition at 1 nM also shown.

FIG. 8 presents in vivo efficacy data for lipid nanoparticle(LNP)-formulated exemplary MYC-targeting duplexes possessing 2′-O-methylmodification patterns of both guide and passenger strands, in micebearing human Hep3B tumors.

FIG. 9 shows in vivo efficacy data for exemplary lipid nanoparticle(LNP)-formulated β-Catenin- and MYC-targeting duplexes, respectively, inmice bearing human HepG2 tumors.

FIG. 10 shows in vivo dose-response knockdown efficacy data for anexemplary lipid nanoparticle (LNP)-formulated MYC-targeting duplex(here, MYC-1711) in mice bearing human Hep3B tumors.

FIG. 11 shows that in vivo duration of effect for an exemplary lipidnanoparticle (LNP)-formulated MYC-targeting duplex (here, MYC-1711) inmice bearing human Hep3B tumors was at least 4 days for miceadministered MYC-1711 at 1 mg/kg, and that significant knockdownpersisted for at least 168 hours when mice were administered MYC-1711 at5 mg/kg.

FIG. 12 shows that lipid nanoparticle (LNP)-formulated MYC-targetingduplex (here, MYC-1711) was a highly effective in vivo anti-tumor agentwhen administered to mice bearing human Hep3B tumors. Notably, suchphenotypic efficacy of MYC-targeting duplexes at producing tumorreduction also exhibited dose-response. (***, P<0.001; ****, P<0.0001)

FIG. 13 shows that MYC-1711 duplexes presenting a number of different2′-O-methyl patterns (here, “M12-M48”, “M32-M48”, “M50-M73” and“M50-M48” patterned duplexes) exhibited significant Hep3B tumorreduction in vivo.

FIG. 14 shows that low-dose DsiRNA administrations (twice-a-week (BIW)or even once-a-week (QW)) were highly effective at reducing Hep3B tumorsize in vivo.

FIG. 15 shows that MYC-targeting DsiRNA (here, MYC-621) exhibitedsignificant reduction of HT29 colon cancer tumor volume in vivo.

FIG. 16 shows that MYC-targeting DsiRNA exhibited significant reductionof MIA PaCa-2 pancreatic cancer tumor volume in vivo.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to compositions that contain nucleicacids, for example double stranded RNA (“dsRNA”), and methods forpreparing them, that are capable of reducing the level and/or expressionof the MYC gene in vivo or in vitro. One of the strands of the dsRNAcontains a region of nucleotide sequence that has a length that rangesfrom 19 to 35 nucleotides that can direct the destruction and/ortranslational inhibition of the targeted MYC transcript.

DEFINITIONS

Unless defined otherwise, all technical and scientific terms used hereinhave the meaning commonly understood by a person skilled in the art towhich this invention belongs. The following references provide one ofskill with a general definition of many of the terms used in thisinvention: Singleton et al., Dictionary of Microbiology and MolecularBiology (2nd ed. 1994); The Cambridge Dictionary of Science andTechnology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R.Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, TheHarper Collins Dictionary of Biology (1991). As used herein, thefollowing terms have the meanings ascribed to them below, unlessspecified otherwise.

The present invention features one or more DsiRNA molecules that canmodulate (e.g., inhibit) MYC expression. The DsiRNAs of the inventionoptionally can be used in combination with modulators of other genesand/or gene products associated with the maintenance or development ofdiseases or disorders associated with MYC misregulation (e.g., tumorformation and/or growth, etc.). The DsiRNA agents of the inventionmodulate MYC RNAs such as those corresponding to the cDNA sequencesreferred to by GenBank Accession Nos. NM_002467.4 (human MYC) andNM_010849.4 (mouse MYC, transcript variant 1), which are referred toherein generally as “MYC.”

The below description of the various aspects and embodiments of theinvention is provided with reference to exemplary MYC RNAs, generallyreferred to herein as MYC. However, such reference is meant to beexemplary only and the various aspects and embodiments of the inventionare also directed to alternate MYC RNAs, such as mutant MYC RNAs oradditional MYC splice variants. Certain aspects and embodiments are alsodirected to other genes involved in MYC pathways, including genes whosemisregulation acts in association with that of MYC (or is affected oraffects MYC regulation) to produce phenotypic effects that may betargeted for treatment (e.g., tumor formation and/or growth, etc.).BAK1, Noxa, BCL2L11, Bcl-2-associated death promoter, PCNA, DAD1, TNKSand BH3 interacting domain death agonist are examples of genes thatinteract with MYC. Such additional genes, including those of pathwaysthat act in coordination with MYC, can be targeted using dsRNA and themethods described herein for use of MYC-targeting dsRNAs. Thus, theinhibition and the effects of such inhibition of the other genes can beperformed as described herein.

The term “MYC” refers to nucleic acid sequences encoding a Myc protein,peptide, or polypeptide (e.g., MYC transcripts, such as the sequences ofMYC Genbank Accession Nos. NM_002467.4 and NM_010849.4). In certainembodiments, the term “MYC” is also meant to include other MYC encodingsequence, such as other MYC isoforms, mutant MYC genes, splice variantsof MYC genes, and MYC gene polymorphisms. The term “MYC” is also used torefer to the polypeptide gene product of a MYC gene/transript, e.g., aMyc protein, peptide, or polypeptide, such as those encoded by MYCGenbank Accession Nos. NP_002458.2 and NP_034979.3.

As used herein, a “MYC-associated disease or disorder” refers to adisease or disorder known in the art to be associated with altered MYCexpression, level and/or activity. Notably, a “MYC-associated disease ordisorder” includes cancer and/or proliferative diseases, conditions, ordisorders. Certain exemplary “MYC-associated disease or disorders”include liver cancer (e.g. hepatocellular carcinoma or HCC), lung cancer(e.g., NSCLC), colorectal cancer, prostate cancer, pancreatic cancer,ovarian cancer, cervical cancer, brain cancer (e.g., glioblastoma),renal cancer (e.g., papillary renal carcinoma), stomach cancer,esophageal cancer, medulloblasoma, thyroid carcinoma, rhabdomyosarcoma,osteosarcoma, squamous cell carcinoma (e.g., oral squamous cellcarcinoma), melanoma, breast cancer, and hematopoietic disorders (e.g.,leukemias and lymphomas, and other immune cell-related disorders). Otherhyperproliferative diseases or disorders may also be targeted,including, e.g., bladder, cervical (uterine), endometrial (uterine),head and neck, and oropharyngeal cancers.

By “proliferative disease” or “cancer” as used herein is meant, adisease, condition, trait, genotype or phenotype characterized byunregulated cell growth or replication as is known in the art; includinghepatocellular carcinoma (HCC), leukemias, for example, acutemyelogenous leukemia (AML), chronic myelogenous leukemia (CML), acutelymphocytic leukemia (ALL), and chronic lymphocytic leukemia, AIDSrelated cancers such as Kaposi's sarcoma; breast cancers; bone cancerssuch as Osteosarcoma, Chondrosarcomas, Ewing's sarcoma, Fibrosarcomas,Giant cell tumors, Adamantinomas, and Chordomas; Brain cancers such asMeningiomas, Glioblastomas, Lower-Grade Astrocytomas,Oligodendrocytomas, Pituitary Tumors, Schwannomas, and Metastatic braincancers; cancers of the head and neck including various lymphomas suchas mantle cell lymphoma, non-Hodgkins lymphoma, adenoma, squamous cellcarcinoma, laryngeal carcinoma, gallbladder and bile duct cancers,cancers of the retina such as retinoblastoma, cancers of the esophagus,gastric cancers, multiple myeloma, ovarian cancer, uterine cancer,thyroid cancer, testicular cancer, endometrial cancer, melanoma,colorectal cancer, bladder cancer, prostate cancer, lung cancer(including non-small cell lung carcinoma), pancreatic cancer, sarcomas,Wilms' tumor, cervical cancer, head and neck cancer, skin cancers,nasopharyngeal carcinoma, liposarcoma, epithelial carcinoma, renal cellcarcinoma, gallbladder adeno carcinoma, parotid adenocarcinoma,endometrial sarcoma, multidrug resistant cancers; and proliferativediseases and conditions, such as neovascularization associated withtumor angiogenesis, macular degeneration (e.g., wet/dry AMD), cornealneovascularization, diabetic retinopathy, neovascular glaucoma, myopicdegeneration and other proliferative diseases and conditions such asrestenosis and polycystic kidney disease, and other cancer orproliferative disease, condition, trait, genotype or phenotype that canrespond to the modulation of disease related gene expression in a cellor tissue, alone or in combination with other therapies.

In certain embodiments, dsRNA-mediated inhibition of a MYC targetsequence is assessed. In such embodiments, MYC RNA levels can beassessed by art-recognized methods (e.g., RT-PCR, Northern blot,expression array, etc.), optionally via comparison of MYC levels in thepresence of an anti-MYC dsRNA of the invention relative to the absenceof such an anti-MYC dsRNA. In certain embodiments, MYC levels in thepresence of an anti-MYC dsRNA are compared to those observed in thepresence of vehicle alone, in the presence of a dsRNA directed againstan unrelated target RNA, or in the absence of any treatment.

It is also recognized that levels of Myc protein can be assessed andthat Myc protein levels are, under different conditions, either directlyor indirectly related to MYC RNA levels and/or the extent to which adsRNA inhibits MYC expression, thus art-recognized methods of assessingMyc protein levels (e.g., Western blot, immunoprecipitation, otherantibody-based methods, etc.) can also be employed to examine theinhibitory effect of a dsRNA of the invention.

An anti-MYC dsRNA of the invention is deemed to possess “MYC inhibitoryactivity” if a statistically significant reduction in MYC RNA (or whenthe Myc protein is assessed, Myc protein levels) is seen when ananti-MYC dsRNA of the invention is administered to a system (e.g.,cell-free in vitro system), cell, tissue or organism, as compared to aselected control. The distribution of experimental values and the numberof replicate assays performed will tend to dictate the parameters ofwhat levels of reduction in MYC RNA (either as a % or in absolute terms)is deemed statistically significant (as assessed by standard methods ofdetermining statistical significance known in the art). However, incertain embodiments, “MYC inhibitory activity” is defined based upon a %or absolute level of reduction in the level of MYC in a system, cell,tissue or organism. For example, in certain embodiments, a dsRNA of theinvention is deemed to possess MYC inhibitory activity if at least a 5%reduction or at least a 10% reduction in MYC RNA is observed in thepresence of a dsRNA of the invention relative to MYC levels seen for asuitable control. (For example, in vivo MYC levels in a tissue and/orsubject can, in certain embodiments, be deemed to be inhibited by adsRNA agent of the invention if, e.g., a 5% or 10% reduction in MYClevels is observed relative to a control.) In certain other embodiments,a dsRNA of the invention is deemed to possess MYC inhibitory activity ifMYC RNA levels are observed to be reduced by at least 15% relative to aselected control, by at least 20% relative to a selected control, by atleast 25% relative to a selected control, by at least 30% relative to aselected control, by at least 35% relative to a selected control, by atleast 40% relative to a selected control, by at least 45% relative to aselected control, by at least 50% relative to a selected control, by atleast 55% relative to a selected control, by at least 60% relative to aselected control, by at least 65% relative to a selected control, by atleast 70% relative to a selected control, by at least 75% relative to aselected control, by at least 80% relative to a selected control, by atleast 85% relative to a selected control, by at least 90% relative to aselected control, by at least 95% relative to a selected control, by atleast 96% relative to a selected control, by at least 97% relative to aselected control, by at least 98% relative to a selected control or byat least 99% relative to a selected control. In some embodiments,complete inhibition of MYC is required for a dsRNA to be deemed topossess MYC inhibitory activity. In certain models (e.g., cell culture),a dsRNA is deemed to possess MYC inhibitory activity if at least a 50%reduction in MYC levels is observed relative to a suitable control. Incertain other embodiments, a dsRNA is deemed to possess MYC inhibitoryactivity if at least an 80% reduction in MYC levels is observed relativeto a suitable control.

By way of specific example, in Example 2 below, a series of DsiRNAstargeting MYC were tested for the ability to reduce MYC mRNA levels inhuman A549 or mouse Hepa 1-6 cells in vitro, at 1 nM concentrations inthe environment of such cells and in the presence of a transfectionagent (Lipofectamine™ RNAiMAX, Invitrogen). Within Example 2 below, MYCinhibitory activity was ascribed to those DsiRNAs that were observed toeffect at least a 70% reduction of MYC mRNA levels under the assayedconditions. It is contemplated that MYC inhibitory activity could alsobe attributed to a dsRNA under either more or less stringent conditionsthan those employed for Example 2 below, even when the same or a similarassay and conditions are employed. For example, in certain embodiments,a tested dsRNA of the invention is deemed to possess MYC inhibitoryactivity if at least a 10% reduction, at least a 20% reduction, at leasta 30% reduction, at least a 40% reduction, at least a 50% reduction, atleast a 60% reduction, at least a 75% reduction, at least an 80%reduction, at least an 85% reduction, at least a 90% reduction, or atleast a 95% reduction in MYC mRNA levels is observed in a mammalian cellline in vitro at 1 nM dsRNA concentration or lower in the environment ofa cell, relative to a suitable control.

Use of other endpoints for determination of whether a double strandedRNA of the invention possesses MYC inhibitory activity is alsocontemplated. Specifically, in one embodiment, in addition to or as analternative to assessing MYC mRNA levels, the ability of a tested dsRNAto reduce Myc protein levels (e.g., at 48 hours after contacting amammalian cell in vitro or in vivo) is assessed, and a tested dsRNA isdeemed to possess MYC inhibitory activity if at least a 10% reduction,at least a 20% reduction, at least a 30% reduction, at least a 40%reduction, at least a 50% reduction, at least a 60% reduction, at leasta 70% reduction, at least a 75% reduction, at least an 80% reduction, atleast an 85% reduction, at least a 90% reduction, or at least a 95%reduction in Myc protein levels is observed in a mammalian cellcontacted with the assayed double stranded RNA in vitro or in vivo,relative to a suitable control. Additional endpoints contemplatedinclude, e.g., assessment of a phenotype associated with reduction ofMYC levels—e.g., reduction of growth of a contacted mammalian cell linein vitro and/or reduction of growth of a tumor in vivo, including, e.g.,halting or reducing the growth of tumor or cancer cell levels asdescribed in greater detail elsewhere herein.

MYC inhibitory activity can also be evaluated over time (duration) andover concentration ranges (potency), with assessment of what constitutesa dsRNA possessing MYC inhibitory activity adjusted in accordance withconcentrations administered and duration of time followingadministration. Thus, in certain embodiments, a dsRNA of the inventionis deemed to possess MYC inhibitory activity if at least a 50% reductionin MYC activity is observed/persists at a duration of time of 2 hours, 5hours, 10 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days,8 days, 9 days, 10 days or more after administration of the dsRNA to acell or organism. In additional embodiments, a dsRNA of the invention isdeemed to be a potent MYC inhibitory agent if MYC inhibitory activity(e.g., in certain embodiments, at least 50% inhibition of MYC) isobserved at a concentration of 1 nM or less, 500 pM or less, 200 pM orless, 100 pM or less, 50 pM or less, 20 pM or less, 10 pM or less, 5 pMor less, 2 pM or less or even 1 pM or less in the environment of a cell,for example, within an in vitro assay for MYC inhibitory activity asdescribed herein. In certain embodiments, a potent MYC inhibitory dsRNAof the invention is defined as one that is capable of MYC inhibitoryactivity (e.g., in certain embodiments, at least 20% reduction of MYClevels) at a formulated concentration of 10 mg/kg or less whenadministered to a subject in an effective delivery vehicle (e.g., aneffective lipid nanoparticle formulation). Preferably, a potent MYCinhibitory dsRNA of the invention is defined as one that is capable ofMYC inhibitory activity (e.g., in certain embodiments, at least 50%reduction of MYC levels) at a formulated concentration of 5 mg/kg orless when administered to a subject in an effective delivery vehicle.More preferably, a potent MYC inhibitory dsRNA of the invention isdefined as one that is capable of MYC inhibitory activity (e.g., incertain embodiments, at least 50% reduction of MYC levels) at aformulated concentration of 5 mg/kg or less when administered to asubject in an effective delivery vehicle. Optionally, a potent MYCinhibitory dsRNA of the invention is defined as one that is capable ofMYC inhibitory activity (e.g., in certain embodiments, at least 50%reduction of MYC levels) at a formulated concentration of 2 mg/kg orless, or even 1 mg/kg or less, when administered to a subject in aneffective delivery vehicle.

In certain embodiments, potency of a dsRNA of the invention isdetermined in reference to the number of copies of a dsRNA present inthe cytoplasm of a target cell that are required to achieve a certainlevel of target gene knockdown. For example, in certain embodiments, apotent dsRNA is one capable of causing 50% or greater knockdown of atarget mRNA when present in the cytoplasm of a target cell at a copynumber of 1000 or fewer RISC-loaded antisense strands per cell. Morepreferably, a potent dsRNA is one capable of producing 50% or greaterknockdown of a target mRNA when present in the cytoplasm of a targetcell at a copy number of 500 or fewer RISC-loaded antisense strands percell. Optionally, a potent dsRNA is one capable of producing 50% orgreater knockdown of a target mRNA when present in the cytoplasm of atarget cell at a copy number of 300 or fewer RISC-loaded antisensestrands per cell.

In further embodiments, the potency of a DsiRNA of the invention can bedefined in reference to a 19 to 23mer dsRNA directed to the same targetsequence within the same target gene. For example, a DsiRNA of theinvention that possesses enhanced potency relative to a corresponding 19to 23mer dsRNA can be a DsiRNA that reduces a target gene by anadditional 5% or more, an additional 10% or more, an additional 20% ormore, an additional 30% or more, an additional 40% or more, or anadditional 50% or more as compared to a corresponding 19 to 23mer dsRNA,when assayed in an in vitro assay as described herein at a sufficientlylow concentration to allow for detection of a potency difference (e.g.,transfection concentrations at or below 1 nM in the environment of acell, at or below 100 pM in the environment of a cell, at or below 10 pMin the environment of a cell, at or below 1 nM in the environment of acell, in an in vitro assay as described herein; notably, it isrecognized that potency differences can be best detected via performanceof such assays across a range of concentrations—e.g., 0.1 pM to 10nM—for purpose of generating a dose-response curve and identifying anIC₅₀ value associated with a DsiRNA/dsRNA).

MYC inhibitory levels and/or MYC levels may also be assessed indirectly,e.g., measurement of a reduction of the size, number and/or rate ofgrowth or spread of polyps or tumors in a subject may be used to assessMYC levels and/or MYC inhibitory efficacy of a double-stranded nucleicacid of the instant invention.

In certain embodiments, the phrase “consists essentially of” is used inreference to the anti-MYC dsRNAs of the invention. In some suchembodiments, “consists essentially of” refers to a composition thatcomprises a dsRNA of the invention which possesses at least a certainlevel of MYC inhibitory activity (e.g., at least 50% MYC inhibitoryactivity) and that also comprises one or more additional componentsand/or modifications that do not significantly impact the MYC inhibitoryactivity of the dsRNA. For example, in certain embodiments, acomposition “consists essentially of” a dsRNA of the invention wheremodifications of the dsRNA of the invention and/or dsRNA-associatedcomponents of the composition do not alter the MYC inhibitory activity(optionally including potency or duration of MYC inhibitory activity) bygreater than 3%, greater than 5%, greater than 10%, greater than 15%,greater than 20%, greater than 25%, greater than 30%, greater than 35%,greater than 40%, greater than 45%, or greater than 50% relative to thedsRNA of the invention in isolation. In certain embodiments, acomposition is deemed to consist essentially of a dsRNA of the inventioneven if more dramatic reduction of MYC inhibitory activity (e.g., 80%reduction, 90% reduction, etc. in efficacy, duration and/or potency)occurs in the presence of additional components or modifications, yetwhere MYC inhibitory activity is not significantly elevated (e.g.,observed levels of MYC inhibitory activity are within 10% those observedfor the isolated dsRNA of the invention) in the presence of additionalcomponents and/or modifications.

As used herein, the term “nucleic acid” refers to deoxyribonucleotides,ribonucleotides, or modified nucleotides, and polymers thereof insingle- or double-stranded form. The term encompasses nucleic acidscontaining known nucleotide analogs or modified backbone residues orlinkages, which are synthetic, naturally occurring, and non-naturallyoccurring, which have similar binding properties as the referencenucleic acid, and which are metabolized in a manner similar to thereference nucleotides. Examples of such analogs include, withoutlimitation, phosphorothioates, phosphoramidates, methyl phosphonates,chiral-methyl phosphonates, 2-O-methyl ribonucleotides, peptide-nucleicacids (PNAs) and unlocked nucleic acids (UNAs; see, e.g., Jensen et al.Nucleic Acids Symposium Series 52: 133-4), and derivatives thereof.

As used herein, “nucleotide” is used as recognized in the art to includethose with natural bases (standard), and modified bases well known inthe art. Such bases are generally located at the 1′ position of anucleotide sugar moiety. Nucleotides generally comprise a base, sugarand a phosphate group. The nucleotides can be unmodified or modified atthe sugar, phosphate and/or base moiety, (also referred tointerchangeably as nucleotide analogs, modified nucleotides, non-naturalnucleotides, non-standard nucleotides and other; see, e.g., Usman andMcSwiggen, supra; Eckstein, et al., International PCT Publication No. WO92/07065; Usman et al, International PCT Publication No. WO 93/15187;Uhlman & Peyman, supra, all are hereby incorporated by referenceherein). There are several examples of modified nucleic acid bases knownin the art as summarized by Limbach, et al, Nucleic Acids Res. 22:2183,1994. Some of the non-limiting examples of base modifications that canbe introduced into nucleic acid molecules include, hypoxanthine, purine,pyridin-4-one, pyridin-2-one, phenyl, pseudouracil, 2,4,6-trimethoxybenzene, 3-methyl uracil, dihydrouridine, naphthyl, aminophenyl,5-alkylcytidines (e.g., 5-methylcytidine), 5-alkyluridines (e.g.,ribothymidine), 5-halouridine (e.g., 5-bromouridine) or 6-azapyrimidinesor 6-alkylpyrimidines (e.g. 6-methyluridine), propyne, and others(Burgin, et al., Biochemistry 35:14090, 1996; Uhlman & Peyman, supra).By “modified bases” in this aspect is meant nucleotide bases other thanadenine, guanine, cytosine and uracil at 1′ position or theirequivalents.

As used herein, “modified nucleotide” refers to a nucleotide that hasone or more modifications to the nucleoside, the nucleobase, pentosering, or phosphate group. For example, modified nucleotides excluderibonucleotides containing adenosine monophosphate, guanosinemonophosphate, uridine monophosphate, and cytidine monophosphate anddeoxyribonucleotides containing deoxyadenosine monophosphate,deoxyguanosine monophosphate, deoxythymidine monophosphate, anddeoxycytidine monophosphate. Modifications include those naturallyoccurring that result from modification by enzymes that modifynucleotides, such as methyltransferases. Modified nucleotides alsoinclude synthetic or non-naturally occurring nucleotides. Synthetic ornon-naturally occurring modifications in nucleotides include those with2′ modifications, e.g., 2′-methoxyethoxy, 2′-fluoro, 2′-allyl,2′-O-[2-(methylamino)-2-oxoethyl], 4′-thio, 4′-CH₂—O-2′-bridge,4′-(CH₂)₂—O-2′-bridge, 2′-LNA or other bicyclic or “bridged” nucleosideanalog, and 2′-O-(N-methylcarbamate) or those comprising base analogs.In connection with 2′-modified nucleotides as described for the presentdisclosure, by “amino” is meant 2′-NH₂ or 2′-O—NH₂, which can bemodified or unmodified. Such modified groups are described, e.g., inEckstein et al., U.S. Pat. No. 5,672,695 and Matulic-Adamic et al., U.S.Pat. No. 6,248,878. “Modified nucleotides” of the instant invention canalso include nucleotide analogs as described above.

In reference to the nucleic acid molecules of the present disclosure,modifications may exist upon these agents in patterns on one or bothstrands of the double stranded ribonucleic acid (dsRNA). As used herein,“alternating positions” refers to a pattern where every other nucleotideis a modified nucleotide or there is an unmodified nucleotide (e.g., anunmodified ribonucleotide) between every modified nucleotide over adefined length of a strand of the dsRNA (e.g., 5′-MNMNMN-3′;3′-MNMNMN-5′; where M is a modified nucleotide and N is an unmodifiednucleotide). The modification pattern starts from the first nucleotideposition at either the 5′ or 3′ terminus according to a positionnumbering convention, e.g., as described herein (in certain embodiments,position 1 is designated in reference to the terminal residue of astrand following a projected Dicer cleavage event of a DsiRNA agent ofthe invention; thus, position 1 does not always constitute a 3′ terminalor 5′ terminal residue of a pre-processed agent of the invention). Thepattern of modified nucleotides at alternating positions may run thefull length of the strand, but in certain embodiments includes at least4, 6, 8, 10, 12, 14 nucleotides containing at least 2, 3, 4, 5, 6 or 7modified nucleotides, respectively. As used herein, “alternating pairsof positions” refers to a pattern where two consecutive modifiednucleotides are separated by two consecutive unmodified nucleotides overa defined length of a strand of the dsRNA (e.g., 5′-MMNNMMNNMMNN-3′;3′-MMNNMMNNMMNN-5′; where M is a modified nucleotide and N is anunmodified nucleotide). The modification pattern starts from the firstnucleotide position at either the 5′ or 3′ terminus according to aposition numbering convention such as those described herein. Thepattern of modified nucleotides at alternating positions may run thefull length of the strand, but preferably includes at least 8, 12, 16,20, 24, 28 nucleotides containing at least 4, 6, 8, 10, 12 or 14modified nucleotides, respectively. It is emphasized that the abovemodification patterns are exemplary and are not intended as limitationson the scope of the invention.

As used herein, “base analog” refers to a heterocyclic moiety which islocated at the 1′ position of a nucleotide sugar moiety in a modifiednucleotide that can be incorporated into a nucleic acid duplex (or theequivalent position in a nucleotide sugar moiety substitution that canbe incorporated into a nucleic acid duplex). In the dsRNAs of theinvention, a base analog is generally either a purine or pyrimidine baseexcluding the common bases guanine (G), cytosine (C), adenine (A),thymine (T), and uracil (U). Base analogs can duplex with other bases orbase analogs in dsRNAs. Base analogs include those useful in thecompounds and methods of the invention, e.g., those disclosed in U.S.Pat. Nos. 5,432,272 and 6,001,983 to Benner and US Patent PublicationNo. 20080213891 to Manoharan, which are herein incorporated byreference. Non-limiting examples of bases include hypoxanthine (I),xanthine (X), 3β-D-ribofuranosyl-(2,6-diaminopyrimidine) (K),3-β-D-ribofuranosyl-(1-methyl-pyrazolo[4,3-d]pyrimidine-5,7(4H,6H)-dione)(P), iso-cytosine (iso-C), iso-guanine (iso-G),1-β-D-ribofuranosyl-(5-nitroindole),1-β-D-ribofuranosyl-(3-nitropyrrole), 5-bromouracil, 2-aminopurine,4-thio-dT, 7-(2-thienyl)-imidazo[4,5-b]pyridine (Ds) andpyrrole-2-carbaldehyde (Pa), 2-amino-6-(2-thienyl)purine (S),2-oxopyridine (Y), difluorotolyl, 4-fluoro-6-methylbenzimidazole,4-methylbenzimidazole, 3-methyl isocarbostyrilyl, 5-methylisocarbostyrilyl, and 3-methyl-7-propynyl isocarbostyrilyl,7-azaindolyl, 6-methyl-7-azaindolyl, imidizopyridinyl,9-methyl-imidizopyridinyl, pyrrolopyrizinyl, isocarbostyrilyl,7-propynyl isocarbostyrilyl, propynyl-7-azaindolyl,2,4,5-trimethylphenyl, 4-methylindolyl, 4,6-dimethylindolyl, phenyl,napthalenyl, anthracenyl, phenanthracenyl, pyrenyl, stilbenzyl,tetracenyl, pentacenyl, and structural derivates thereof (Schweitzer etal., J. Org. Chem., 59:7238-7242 (1994); Berger et al., Nucleic AcidsResearch, 28(15):2911-2914 (2000); Moran et al., J. Am. Chem. Soc.,119:2056-2057 (1997); Morales et al., J. Am. Chem. Soc., 121:2323-2324(1999); Guckian et al., J. Am. Chem. Soc., 118:8182-8183 (1996); Moraleset al., J. Am. Chem. Soc., 122(6):1001-1007 (2000); McMinn et al., J.Am. Chem. Soc., 121:11585-11586 (1999); Guckian et al., J. Org. Chem.,63:9652-9656 (1998); Moran et al., Proc. Natl. Acad. Sci.,94:10506-10511 (1997); Das et al., J. Chem. Soc., Perkin Trans.,1:197-206 (2002); Shibata et al., J. Chem. Soc., Perkin Trans., 1:1605-1611 (2001); Wu et al., J. Am. Chem. Soc., 122(32):7621-7632(2000); O'Neill et al., J. Org. Chem., 67:5869-5875 (2002); Chaudhuri etal., J. Am. Chem. Soc., 117:10434-10442 (1995); and U.S. Pat. No.6,218,108.). Base analogs may also be a universal base.

As used herein, “universal base” refers to a heterocyclic moiety locatedat the 1′ position of a nucleotide sugar moiety in a modifiednucleotide, or the equivalent position in a nucleotide sugar moietysubstitution, that, when present in a nucleic acid duplex, can bepositioned opposite more than one type of base without altering thedouble helical structure (e.g., the structure of the phosphatebackbone). Additionally, the universal base does not destroy the abilityof the single stranded nucleic acid in which it resides to duplex to atarget nucleic acid. The ability of a single stranded nucleic acidcontaining a universal base to duplex a target nucleic can be assayed bymethods apparent to one in the art (e.g., UV absorbance, circulardichroism, gel shift, single stranded nuclease sensitivity, etc.).Additionally, conditions under which duplex formation is observed may bevaried to determine duplex stability or formation, e.g., temperature, asmelting temperature (Tm) correlates with the stability of nucleic acidduplexes. Compared to a reference single stranded nucleic acid that isexactly complementary to a target nucleic acid, the single strandednucleic acid containing a universal base forms a duplex with the targetnucleic acid that has a lower Tm than a duplex formed with thecomplementary nucleic acid. However, compared to a reference singlestranded nucleic acid in which the universal base has been replaced witha base to generate a single mismatch, the single stranded nucleic acidcontaining the universal base forms a duplex with the target nucleicacid that has a higher Tm than a duplex formed with the nucleic acidhaving the mismatched base.

Some universal bases are capable of base pairing by forming hydrogenbonds between the universal base and all of the bases guanine (G),cytosine (C), adenine (A), thymine (T), and uracil (U) under base pairforming conditions. A universal base is not a base that forms a basepair with only one single complementary base. In a duplex, a universalbase may form no hydrogen bonds, one hydrogen bond, or more than onehydrogen bond with each of G, C, A, T, and U opposite to it on theopposite strand of a duplex. Preferably, the universal bases does notinteract with the base opposite to it on the opposite strand of aduplex. In a duplex, base pairing between a universal base occurswithout altering the double helical structure of the phosphate backbone.A universal base may also interact with bases in adjacent nucleotides onthe same nucleic acid strand by stacking interactions. Such stackinginteractions stabilize the duplex, especially in situations where theuniversal base does not form any hydrogen bonds with the base positionedopposite to it on the opposite strand of the duplex. Non-limitingexamples of universal-binding nucleotides include inosine,1-β-D-ribofuranosyl-5-nitroindole, and/or1β-D-ribofuranosyl-3-nitropyrrole (US Pat. Appl. Publ. No. 20070254362to Quay et al.; Van Aerschot et al., An acyclic 5-nitroindazolenucleoside analogue as ambiguous nucleoside. Nucleic Acids Res. 1995Nov. 11; 23(21):4363-70; Loakes et al., 3-Nitropyrrole and 5-nitroindoleas universal bases in primers for DNA sequencing and PCR. Nucleic AcidsRes. 1995 Jul. 11; 23(13):2361-6; Loakes and Brown, 5-Nitroindole as anuniversal base analogue. Nucleic Acids Res. 1994 Oct. 11;22(20):4039-43).

As used herein, “loop” refers to a structure formed by a single strandof a nucleic acid, in which complementary regions that flank aparticular single stranded nucleotide region hybridize in a way that thesingle stranded nucleotide region between the complementary regions isexcluded from duplex formation or Watson-Crick base pairing. A loop is asingle stranded nucleotide region of any length. Examples of loopsinclude the unpaired nucleotides present in such structures as hairpins,stem loops, or extended loops.

As used herein, “extended loop” in the context of a dsRNA refers to asingle stranded loop and in addition 1, 2, 3, 4, 5, 6 or up to 20 basepairs or duplexes flanking the loop. In an extended loop, nucleotidesthat flank the loop on the 5′ side form a duplex with nucleotides thatflank the loop on the 3′ side. An extended loop may form a hairpin orstem loop.

As used herein, “tetraloop” in the context of a dsRNA refers to a loop(a single stranded region) consisting of four nucleotides that forms astable secondary structure that contributes to the stability of anadjacent Watson-Crick hybridized nucleotides. Without being limited totheory, a tetraloop may stabilize an adjacent Watson-Crick base pair bystacking interactions. In addition, interactions among the fournucleotides in a tetraloop include but are not limited tonon-Watson-Crick base pairing, stacking interactions, hydrogen bonding,and contact interactions (Cheong et al., Nature 1990 Aug. 16;346(6285):680-2; Heus and Pardi, Science 1991 Jul. 12; 253(5016):191-4).A tetraloop confers an increase in the melting temperature (Tm) of anadjacent duplex that is higher than expected from a simple model loopsequence consisting of four random bases. For example, a tetraloop canconfer a melting temperature of at least 55° C. in 10 mM NaHPO₄ to ahairpin comprising a duplex of at least 2 base pairs in length. Atetraloop may contain ribonucleotides, deoxyribonucleotides, modifiednucleotides, and combinations thereof. Examples of RNA tetraloopsinclude the UNCG family of tetraloops (e.g., UUCG), the GNRA family oftetraloops (e.g., GAAA), and the CUUG tetraloop. (Woese et al., ProcNatl Acad Sci USA. 1990 November; 87(21):8467-71; Antao et al., NucleicAcids Res. 1991 Nov. 11; 19(21):5901-5). Examples of DNA tetraloopsinclude the d(GNNA) family of tetraloops (e.g., d(GTTA), the d(GNRA))family of tetraloops, the d(GNAB) family of tetraloops, the d(CNNG)family of tetraloops, the d(TNCG) family of tetraloops (e.g., d(TTCG)).(Nakano et al. Biochemistry, 41 (48), 14281-14292, 2002.; SHINJI et al.Nippon Kagakkai Koen Yokoshu VOL. 78th; NO. 2; PAGE. 731 (2000).)

As used herein, the term “siRNA” refers to a double stranded nucleicacid in which each strand comprises RNA, RNA analog(s) or RNA and DNA.The siRNA comprises between 19 and 23 nucleotides or comprises 21nucleotides. The siRNA typically has 2 bp overhangs on the 3′ ends ofeach strand such that the duplex region in the siRNA comprises 17-21nucleotides, or 19 nucleotides. Typically, the antisense strand of thesiRNA is sufficiently complementary with the target sequence of the MYCgene/RNA.

An anti-MYC DsiRNA of the instant invention possesses strand lengths ofat least 25 nucleotides. Accordingly, in certain embodiments, ananti-MYC DsiRNA contains one oligonucleotide sequence, a first sequence,that is at least 25 nucleotides in length and no longer than 35 or up to50 or more nucleotides. This sequence of RNA can be between 26 and 35,26 and 34, 26 and 33, 26 and 32, 26 and 31, 26 and 30, and 26 and 29nucleotides in length. This sequence can be 27 or 28 nucleotides inlength or 27 nucleotides in length. The second sequence of the DsiRNAagent can be a sequence that anneals to the first sequence underbiological conditions, such as within the cytoplasm of a eukaryoticcell. Generally, the second oligonucleotide sequence will have at least19 complementary base pairs with the first oligonucleotide sequence,more typically the second oligonucleotide sequence will have 21 or morecomplementary base pairs, or 25 or more complementary base pairs withthe first oligonucleotide sequence. In one embodiment, the secondsequence is the same length as the first sequence, and the DsiRNA agentis blunt ended. In another embodiment, the ends of the DsiRNA agent haveone or more overhangs.

In certain embodiments, the first and second oligonucleotide sequencesof the DsiRNA agent exist on separate oligonucleotide strands that canbe and typically are chemically synthesized. In some embodiments, bothstrands are between 26 and 35 nucleotides in length. In otherembodiments, both strands are between 25 and 30 or 26 and 30 nucleotidesin length. In one embodiment, both strands are 27 nucleotides in length,are completely complementary and have blunt ends. In certain embodimentsof the instant invention, the first and second sequences of an anti-MYCDsiRNA exist on separate RNA oligonucleotides (strands). In oneembodiment, one or both oligonucleotide strands are capable of servingas a substrate for Dicer. In other embodiments, at least onemodification is present that promotes Dicer to bind to thedouble-stranded RNA structure in an orientation that maximizes thedouble-stranded RNA structure's effectiveness in inhibiting geneexpression. In certain embodiments of the instant invention, theanti-MYC DsiRNA agent is comprised of two oligonucleotide strands ofdiffering lengths, with the anti-MYC DsiRNA possessing a blunt end atthe 3′ terminus of a first strand (sense strand) and a 3′ overhang atthe 3′ terminus of a second strand (antisense strand). The DsiRNA canalso contain one or more deoxyribonucleic acid (DNA) base substitutions.

Suitable DsiRNA compositions that contain two separate oligonucleotidescan be chemically linked outside their annealing region by chemicallinking groups. Many suitable chemical linking groups are known in theart and can be used. Suitable groups will not block Dicer activity onthe DsiRNA and will not interfere with the directed destruction of theRNA transcribed from the target gene. Alternatively, the two separateoligonucleotides can be linked by a third oligonucleotide such that ahairpin structure is produced upon annealing of the two oligonucleotidesmaking up the DsiRNA composition. The hairpin structure will not blockDicer activity on the DsiRNA and will not interfere with the directeddestruction of the target RNA.

As used herein, a dsRNA, e.g., DsiRNA or siRNA, having a sequence“sufficiently complementary” to a target RNA or cDNA sequence (e.g., MYCmRNA) means that the dsRNA has a sequence sufficient to trigger thedestruction of the target RNA (where a cDNA sequence is recited, the RNAsequence corresponding to the recited cDNA sequence) by the RNAimachinery (e.g., the RISC complex) or process. For example, a dsRNA thatis “sufficiently complementary” to a target RNA or cDNA sequence totrigger the destruction of the target RNA by the RNAi machinery orprocess can be identified as a dsRNA that causes a detectable reductionin the level of the target RNA in an appropriate assay of dsRNA activity(e.g., an in vitro assay as described in Example 2 below), or, infurther examples, a dsRNA that is sufficiently complementary to a targetRNA or cDNA sequence to trigger the destruction of the target RNA by theRNAi machinery or process can be identified as a dsRNA that produces atleast a 5%, at least a 10%, at least a 15%, at least a 20%, at least a25%, at least a 30%, at least a 35%, at least a 40%, at least a 45%, atleast a 50%, at least a 55%, at least a 60%, at least a 65%, at least a70%, at least a 75%, at least a 80%, at least a 85%, at least a 90%, atleast a 95%, at least a 98% or at least a 99% reduction in the level ofthe target RNA in an appropriate assay of dsRNA activity. In additionalexamples, a dsRNA that is sufficiently complementary to a target RNA orcDNA sequence to trigger the destruction of the target RNA by the RNAimachinery or process can be identified based upon assessment of theduration of a certain level of inhibitory activity with respect to thetarget RNA or protein levels in a cell or organism. For example, a dsRNAthat is sufficiently complementary to a target RNA or cDNA sequence totrigger the destruction of the target RNA by the RNAi machinery orprocess can be identified as a dsRNA capable of reducing target mRNAlevels by at least 20% at least 48 hours post-administration of saiddsRNA to a cell or organism. Preferably, a dsRNA that is sufficientlycomplementary to a target RNA or cDNA sequence to trigger thedestruction of the target RNA by the RNAi machinery or process isidentified as a dsRNA capable of reducing target mRNA levels by at least40% at least 72 hours post-administration of said dsRNA to a cell ororganism, by at least 40% at least four, five or seven dayspost-administration of said dsRNA to a cell or organism, by at least 50%at least 48 hours post-administration of said dsRNA to a cell ororganism, by at least 50% at least 72 hours post-administration of saiddsRNA to a cell or organism, by at least 50% at least four, five orseven days post-administration of said dsRNA to a cell or organism, byat least 80% at least 48 hours post-administration of said dsRNA to acell or organism, by at least 80% at least 72 hours post-administrationof said dsRNA to a cell or organism, or by at least 80% at least four,five or seven days post-administration of said dsRNA to a cell ororganism.

The dsRNA molecule can be designed such that every residue of theantisense strand is complementary to a residue in the target molecule.Alternatively, substitutions can be made within the molecule to increasestability and/or enhance processing activity of said molecule.Substitutions can be made within the strand or can be made to residuesat the ends of the strand. In certain embodiments, substitutions and/ormodifications are made at specific residues within a DsiRNA agent. Suchsubstitutions and/or modifications can include, e.g.,deoxy-modifications at one or more residues of positions 1, 2 and 3 whennumbering from the 3′ terminal position of the sense strand of a DsiRNAagent; and introduction of 2′-O-alkyl (e.g., 2′-O-methyl) modificationsat the 3′ terminal residue of the antisense strand of DsiRNA agents,with such modifications also being performed at overhang positions ofthe 3′ portion of the antisense strand and at alternating residues ofthe antisense strand of the DsiRNA that are included within the regionof a DsiRNA agent that is processed to form an active siRNA agent. Thepreceding modifications are offered as exemplary, and are not intendedto be limiting in any manner. Further consideration of the structure ofpreferred DsiRNA agents, including further description of themodifications and substitutions that can be performed upon the anti-MYCDsiRNA agents of the instant invention, can be found below.

Where a first sequence is referred to as “substantially complementary”with respect to a second sequence herein, the two sequences can be fullycomplementary, or they may form one or more, but generally not more than4, 3 or 2 mismatched base pairs upon hybridization, while retaining theability to hybridize under the conditions most relevant to theirultimate application. However, where two oligonucleotides are designedto form, upon hybridization, one or more single stranded overhangs, suchoverhangs shall not be regarded as mismatches with regard to thedetermination of complementarity. For example, a dsRNA comprising oneoligonucleotide 21 nucleotides in length and another oligonucleotide 23nucleotides in length, wherein the longer oligonucleotide comprises asequence of 21 nucleotides that is fully complementary to the shorteroligonucleotide, may yet be referred to as “fully complementary” for thepurposes of the invention.

The term “double-stranded RNA” or “dsRNA”, as used herein, refers to acomplex of ribonucleic acid molecules, having a duplex structurecomprising two anti-parallel and substantially complementary, as definedabove, nucleic acid strands. The two strands forming the duplexstructure may be different portions of one larger RNA molecule, or theymay be separate RNA molecules. Where separate RNA molecules, such dsRNAare often referred to as siRNA (“short interfering RNA”) or DsiRNA(“Dicer substrate siRNAs”). Where the two strands are part of one largermolecule, and therefore are connected by an uninterrupted chain ofnucleotides between the 3′-end of one strand and the 5′ end of therespective other strand forming the duplex structure, the connecting RNAchain is referred to as a “hairpin loop”, “short hairpin RNA” or“shRNA”. Where the two strands are connected covalently by means otherthan an uninterrupted chain of nucleotides between the 3′-end of onestrand and the 5′end of the respective other strand forming the duplexstructure, the connecting structure is referred to as a “linker”. TheRNA strands may have the same or a different number of nucleotides. Themaximum number of base pairs is the number of nucleotides in theshortest strand of the dsRNA minus any overhangs that are present in theduplex. In addition to the duplex structure, a dsRNA may comprise one ormore nucleotide overhangs. In addition, as used herein, “dsRNA” mayinclude chemical modifications to ribonucleotides, internucleosidelinkages, end-groups, caps, and conjugated moieties, includingsubstantial modifications at multiple nucleotides and including alltypes of modifications disclosed herein or known in the art. Any suchmodifications, as used in an siRNA- or DsiRNA-type molecule, areencompassed by “dsRNA” for the purposes of this specification andclaims.

The phrase “duplex region” refers to the region in two complementary orsubstantially complementary oligonucleotides that form base pairs withone another, either by Watson-Crick base pairing or other manner thatallows for a duplex between oligonucleotide strands that arecomplementary or substantially complementary. For example, anoligonucleotide strand having 21 nucleotide units can base pair withanother oligonucleotide of 21 nucleotide units, yet only 19 bases oneach strand are complementary or substantially complementary, such thatthe “duplex region” consists of 19 base pairs. The remaining base pairsmay, for example, exist as 5′ and 3′ overhangs. Further, within theduplex region, 100% complementarity is not required; substantialcomplementarity is allowable within a duplex region. Substantialcomplementarity refers to complementarity between the strands such thatthey are capable of annealing under biological conditions. Techniques toempirically determine if two strands are capable of annealing underbiological conditions are well know in the art. Alternatively, twostrands can be synthesized and added together under biologicalconditions to determine if they anneal to one another.

Single-stranded nucleic acids that base pair over a number of bases aresaid to “hybridize.” Hybridization is typically determined underphysiological or biologically relevant conditions (e.g., intracellular:pH 7.2, 140 mM potassium ion; extracellular pH 7.4, 145 mM sodium ion).Hybridization conditions generally contain a monovalent cation andbiologically acceptable buffer and may or may not contain a divalentcation, complex anions, e.g. gluconate from potassium gluconate,uncharged species such as sucrose, and inert polymers to reduce theactivity of water in the sample, e.g. PEG. Such conditions includeconditions under which base pairs can form.

Hybridization is measured by the temperature required to dissociatesingle stranded nucleic acids forming a duplex, i.e., (the meltingtemperature; Tm). Hybridization conditions are also conditions underwhich base pairs can form. Various conditions of stringency can be usedto determine hybridization (see, e.g., Wahl, G. M. and S. L. Berger(1987) Methods Enzymol. 152:399; Kimmel, A. R. (1987) Methods Enzymol.152:507). Stringent temperature conditions will ordinarily includetemperatures of at least about 30° C., more preferably of at least about37° C., and most preferably of at least about 42° C. The hybridizationtemperature for hybrids anticipated to be less than 50 base pairs inlength should be 5-10° C. less than the melting temperature (Tm) of thehybrid, where Tm is determined according to the following equations. Forhybrids less than 18 base pairs in length, Tm(° C.)=2(# of A+Tbases)+4(# of G+C bases). For hybrids between 18 and 49 base pairs inlength, Tm(° C.)=81.5+16.6(log 10[Na+])+0.41 (% G+C)−(600/N), where N isthe number of bases in the hybrid, and [Na+] is the concentration ofsodium ions in the hybridization buffer ([Na+] for 1×SSC=0.165 M). Forexample, a hybridization determination buffer is shown in Table 1.

TABLE 1 To make 50 final conc. Vender Cat# Lot# m.w./Stock mL solutionNaCl 100 mM Sigma S-5150 41K8934 5M 1 mL KCl 80 mM Sigma P-9541 70K0002 74.55 0.298 g MgCl₂ 8 mM Sigma M-1028 120K8933 1M 0.4 mL sucrose 2% w/vFisher BP220-212 907105 342.3 1 g Tris-HCl 16 mM Fisher BP1757-500 124191M 0.8 mL NaH₂PO₄ 1 mM Sigma S-3193 52H-029515 120.0 0.006 g EDTA 0.02mM Sigma E-7889 110K89271 0.5M   2 μL H₂O Sigma W-4502 51K2359 to 50 mLpH = 7.0 adjust with HCl at 20° C.

Useful variations on hybridization conditions will be readily apparentto those skilled in the art. Hybridization techniques are well known tothose skilled in the art and are described, for example, in Benton andDavis (Science 196:180, 1977); Grunstein and Hogness (Proc. Natl. Acad.Sci., USA 72:3961, 1975); Ausubel et al. (Current Protocols in MolecularBiology, Wiley Interscience, New York, 2001); Berger and Kimmel(Antisense to Molecular Cloning Techniques, 1987, Academic Press, NewYork); and Sambrook et al., Molecular Cloning: A Laboratory Manual, ColdSpring Harbor Laboratory Press, New York.

As used herein, “oligonucleotide strand” is a single stranded nucleicacid molecule. An oligonucleotide may comprise ribonucleotides,deoxyribonucleotides, modified nucleotides (e.g., nucleotides with 2′modifications, synthetic base analogs, etc.) or combinations thereof.Such modified oligonucleotides can be preferred over native formsbecause of properties such as, for example, enhanced cellular uptake andincreased stability in the presence of nucleases.

As used herein, the term “ribonucleotide” encompasses natural andsynthetic, unmodified and modified ribonucleotides. Modificationsinclude changes to the sugar moiety, to the base moiety and/or to thelinkages between ribonucleotides in the oligonucleotide. As used herein,the term “ribonucleotide” specifically excludes a deoxyribonucleotide,which is a nucleotide possessing a single proton group at the 2′ ribosering position.

As used herein, the term “deoxyribonucleotide” encompasses natural andsynthetic, unmodified and modified deoxyribonucleotides. Modificationsinclude changes to the sugar moiety, to the base moiety and/or to thelinkages between deoxyribonucleotide in the oligonucleotide. As usedherein, the term “deoxyribonucleotide” also includes a modifiedribonucleotide that does not permit Dicer cleavage of a dsRNA agent,e.g., a 2′-O-methyl ribonucleotide, a phosphorothioate-modifiedribonucleotide residue, etc., that does not permit Dicer cleavage tooccur at a bond of such a residue.

As used herein, the term “PS-NA” refers to a phosphorothioate-modifiednucleotide residue. The term “PS-NA” therefore encompasses bothphosphorothioate-modified ribonucleotides (“PS-RNAs”) andphosphorothioate-modified deoxyribonucleotides (“PS-DNAs”).

As used herein, “Dicer” refers to an endoribonuclease in the RNase IIIfamily that cleaves a dsRNA or dsRNA-containing molecule, e.g.,double-stranded RNA (dsRNA) or pre-microRNA (miRNA), intodouble-stranded nucleic acid fragments 19-25 nucleotides long, usuallywith a two-base overhang on the 3′ end. With respect to certain dsRNAsof the invention (e.g., “DsiRNAs”), the duplex formed by a dsRNA regionof an agent of the invention is recognized by Dicer and is a Dicersubstrate on at least one strand of the duplex. Dicer catalyzes thefirst step in the RNA interference pathway, which consequently resultsin the degradation of a target RNA. The protein sequence of human Diceris provided at the NCBI database under accession number NP_085124,hereby incorporated by reference.

Dicer “cleavage” can be determined as follows (e.g., see Collingwood etal., Oligonucleotides 18:187-200 (2008)). In a Dicer cleavage assay, RNAduplexes (100 pmol) are incubated in 20 μL of 20 mM Tris pH 8.0, 200 mMNaCl, 2.5 mM MgCl2 with or without 1 unit of recombinant human Dicer(Stratagene, La Jolla, Calif.) at 37° C. for 18-24 hours. Samples aredesalted using a Performa SR 96-well plate (Edge Biosystems,Gaithersburg, Md.). Electrospray-ionization liquid chromatography massspectroscopy (ESI-LCMS) of duplex RNAs pre- and post-treatment withDicer is done using an Oligo HTCS system (Novatia, Princeton, N.J.; Hailet al., 2004), which consists of a ThermoFinnigan TSQ7000, Xcalibur datasystem, ProMass data processing software and Paradigm MS4 HPLC (MichromBioResources, Auburn, Calif.). In this assay, Dicer cleavage occurswhere at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, oreven 100% of the Dicer substrate dsRNA, (i.e., 25-30 bp, dsRNA,preferably 26-30 bp dsRNA) is cleaved to a shorter dsRNA (e.g., 19-23 bpdsRNA, preferably, 21-23 bp dsRNA).

As used herein, “Dicer cleavage site” refers to the sites at which Dicercleaves a dsRNA (e.g., the dsRNA region of a DsiRNA agent of theinvention). Dicer contains two RNase III domains which typically cleaveboth the sense and antisense strands of a dsRNA. The average distancebetween the RNase III domains and the PAZ domain determines the lengthof the short double-stranded nucleic acid fragments it produces and thisdistance can vary (Macrae et al. (2006) Science 311: 195-8). As shown inFIG. 1, Dicer is projected to cleave certain double-stranded ribonucleicacids of the instant invention that possess an antisense strand having a2 nucleotide 3′ overhang at a site between the 21^(st) and 22^(nd)nucleotides removed from the 3′ terminus of the antisense strand, and ata corresponding site between the 21^(st) and 22^(nd) nucleotides removedfrom the 5′ terminus of the sense strand. The projected and/or prevalentDicer cleavage site(s) for dsRNA molecules distinct from those depictedin FIG. 1 may be similarly identified via art-recognized methods,including those described in Macrae et al. While the Dicer cleavageevents depicted in FIG. 1 generate 21 nucleotide siRNAs, it is notedthat Dicer cleavage of a dsRNA (e.g., DsiRNA) can result in generationof Dicer-processed siRNA lengths of 19 to 23 nucleotides in length.Indeed, in certain embodiments, a double-stranded DNA region may beincluded within a dsRNA for purpose of directing prevalent Dicerexcision of a typically non-preferred 19mer or 20mer siRNA, rather thana 21mer.

As used herein, “overhang” refers to unpaired nucleotides, in thecontext of a duplex having one or more free ends at the 5′ terminus or3′ terminus of a dsRNA. In certain embodiments, the overhang is a 3′ or5′ overhang on the antisense strand or sense strand. In someembodiments, the overhang is a 3′ overhang having a length of betweenone and six nucleotides, optionally one to five, one to four, one tothree, one to two, two to six, two to five, two to four, two to three,three to six, three to five, three to four, four to six, four to five,five to six nucleotides, or one, two, three, four, five or sixnucleotides. “Blunt” or “blunt end” means that there are no unpairednucleotides at that end of the dsRNA, i.e., no nucleotide overhang. Forclarity, chemical caps or non-nucleotide chemical moieties conjugated tothe 3′ end or 5′ end of an siRNA are not considered in determiningwhether an siRNA has an overhang or is blunt ended. In certainembodiments, the invention provides a dsRNA molecule for inhibiting theexpression of the MYC target gene in a cell or mammal, wherein the dsRNAcomprises an antisense strand comprising a region of complementaritywhich is complementary to at least a part of an mRNA formed in theexpression of the MYC target gene, and wherein the region ofcomplementarity is less than 35 nucleotides in length, optionally 19-24nucleotides in length or 25-30 nucleotides in length, and wherein thedsRNA, upon contact with a cell expressing the MYC target gene, inhibitsthe expression of the MYC target gene by at least 10%, 25%, or 40%.

A dsRNA of the invention comprises two RNA strands that are sufficientlycomplementary to hybridize to form a duplex structure. One strand of thedsRNA (the antisense strand) comprises a region of complementarity thatis substantially complementary, and generally fully complementary, to atarget sequence, derived from the sequence of an mRNA formed during theexpression of the MYC target gene, the other strand (the sense strand)comprises a region which is complementary to the antisense strand, suchthat the two strands hybridize and form a duplex structure when combinedunder suitable conditions. Generally, the duplex structure is between 15and 35, optionally between 25 and 30, between 26 and 30, between 18 and25, between 19 and 24, or between 19 and 21 base pairs in length.Similarly, the region of complementarity to the target sequence isbetween 15 and 35, optionally between 18 and 30, between 25 and 30,between 19 and 24, or between 19 and 21 nucleotides in length. The dsRNAof the invention may further comprise one or more single-strandednucleotide overhang(s). It has been identified that dsRNAs comprisingduplex structures of between 15 and 35 base pairs in length can beeffective in inducing RNA interference, including DsiRNAs (generally ofat least 25 base pairs in length) and siRNAs (in certain embodiments,duplex structures of siRNAs are between 20 and 23, and optionally,specifically 21 base pairs (Elbashir et al., EMBO 20: 6877-6888)). Ithas also been identified that dsRNAs possessing duplexes shorter than 20base pairs can be effective as well (e.g., 15, 16, 17, 18 or 19 basepair duplexes). In certain embodiments, the dsRNAs of the invention cancomprise at least one strand of a length of 19 nucleotides or more. Incertain embodiments, it can be reasonably expected that shorter dsRNAscomprising a sequence complementary to one of the sequences of Table 5,minus only a few nucleotides on one or both ends may be similarlyeffective as compared to the dsRNAs described above and in Tables 2-4and 6-7. Hence, dsRNAs comprising a partial sequence of at least 15, 16,17, 18, 19, 20, or more contiguous nucleotides sufficientlycomplementary to one of the sequences of Table 5, and differing in theirability to inhibit the expression of the MYC target gene in an assay asdescribed herein by not more than 5, 10, 15, 20, 25, or 30% inhibitionfrom a dsRNA comprising the full sequence, are contemplated by theinvention. In one embodiment, at least one end of the dsRNA has asingle-stranded nucleotide overhang of 1 to 5, optionally 1 to 4, incertain embodiments, 1 or 2 nucleotides. Certain dsRNA structures havingat least one nucleotide overhang possess superior inhibitory propertiesas compared to counterparts possessing base-paired blunt ends at bothends of the dsRNA molecule.

As used herein, the term “RNA processing” refers to processingactivities performed by components of the siRNA, miRNA or RNase Hpathways (e.g., Drosha, Dicer, Argonaute2 or other RISCendoribonucleases, and RNaseH), which are described in greater detailbelow (see “RNA Processing” section below). The term is explicitlydistinguished from the post-transcriptional processes of 5′ capping ofRNA and degradation of RNA via non-RISC- or non-RNase H-mediatedprocesses. Such “degradation” of an RNA can take several forms, e.g.deadenylation (removal of a 3′ poly(A) tail), and/or nuclease digestionof part or all of the body of the RNA by one or more of several endo- orexo-nucleases (e.g., RNase III, RNase P, RNase T1, RNase A (1, 2, 3,4/5), oligonucleotidase, etc.).

By “homologous sequence” is meant a nucleotide sequence that is sharedby one or more polynucleotide sequences, such as genes, gene transcriptsand/or non-coding polynucleotides. For example, a homologous sequencecan be a nucleotide sequence that is shared by two or more genesencoding related but different proteins, such as different members of agene family, different protein epitopes, different protein isoforms orcompletely divergent genes, such as a cytokine and its correspondingreceptors. A homologous sequence can be a nucleotide sequence that isshared by two or more non-coding polynucleotides, such as noncoding DNAor RNA, regulatory sequences, introns, and sites of transcriptionalcontrol or regulation. Homologous sequences can also include conservedsequence regions shared by more than one polynucleotide sequence.Homology does not need to be perfect homology (e.g., 100%), as partiallyhomologous sequences are also contemplated by the instant invention(e.g., 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, 90%, 89%, 88%, 87%,86%, 85%, 84%, 83%, 82%, 81%, 80% etc.). Indeed, design and use of thedsRNA agents of the instant invention contemplates the possibility ofusing such dsRNA agents not only against target RNAs of MYC possessingperfect complementarity with the presently described dsRNA agents, butalso against target MYC RNAs possessing sequences that are, e.g., only99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, 90%, 89%, 88%, 87%, 86%,85%, 84%, 83%, 82%, 81%, 80% etc. complementary to said dsRNA agents.Similarly, it is contemplated that the presently described dsRNA agentsof the instant invention might be readily altered by the skilled artisanto enhance the extent of complementarity between said dsRNA agents and atarget MYC RNA, e.g., of a specific allelic variant of MYC (e.g., anallele of enhanced therapeutic interest). Indeed, dsRNA agent sequenceswith insertions, deletions, and single point mutations relative to thetarget MYC sequence can also be effective for inhibition. Alternatively,dsRNA agent sequences with nucleotide analog substitutions or insertionscan be effective for inhibition.

Sequence identity may be determined by sequence comparison and alignmentalgorithms known in the art. To determine the percent identity of twonucleic acid sequences (or of two amino acid sequences), the sequencesare aligned for comparison purposes (e.g., gaps can be introduced in thefirst sequence or second sequence for optimal alignment). Thenucleotides (or amino acid residues) at corresponding nucleotide (oramino acid) positions are then compared. When a position in the firstsequence is occupied by the same residue as the corresponding positionin the second sequence, then the molecules are identical at thatposition. The percent identity between the two sequences is a functionof the number of identical positions shared by the sequences (i.e., %homology=# of identical positions/total # of positions×100), optionallypenalizing the score for the number of gaps introduced and/or length ofgaps introduced.

The comparison of sequences and determination of percent identitybetween two sequences can be accomplished using a mathematicalalgorithm. In one embodiment, the alignment generated over a certainportion of the sequence aligned having sufficient identity but not overportions having low degree of identity (i.e., a local alignment). Apreferred, non-limiting example of a local alignment algorithm utilizedfor the comparison of sequences is the algorithm of Karlin and Altschul(1990) Proc. Natl. Acad. Sci. USA 87:2264-68, modified as in Karlin andAltschul (1993) Proc. Natl. Acad. Sci. USA 90:5873-77. Such an algorithmis incorporated into the BLAST programs (version 2.0) of Altschul, etal. (1990) J. Mol. Biol. 215:403-10.

In another embodiment, a gapped alignment the alignment is optimized isformed by introducing appropriate gaps, and percent identity isdetermined over the length of the aligned sequences (i.e., a gappedalignment). To obtain gapped alignments for comparison purposes, GappedBLAST can be utilized as described in Altschul et al., (1997) NucleicAcids Res. 25(17):3389-3402. In another embodiment, a global alignmentthe alignment is optimizedis formed by introducing appropriate gaps, andpercent identity is determined over the entire length of the sequencesaligned. (i.e., a global alignment). A preferred, non-limiting exampleof a mathematical algorithm utilized for the global comparison ofsequences is the algorithm of Myers and Miller, CABIOS (1989). Such analgorithm is incorporated into the ALIGN program (version 2.0) which ispart of the GCG sequence alignment software package. When utilizing theALIGN program for comparing amino acid sequences, a PAM120 weightresidue table, a gap length penalty of 12, and a gap penalty of 4 can beused.

Greater than 80% sequence identity, e.g., 80%, 81%, 82%, 83%, 84%, 85%,86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% oreven 100% sequence identity, between the dsRNA antisense strand and theportion of the MYC RNA sequence is preferred. Alternatively, the dsRNAmay be defined functionally as a nucleotide sequence (or oligonucleotidesequence) that is capable of hybridizing with a portion of the MYC RNA(e.g., 400 mM NaCl, 40 mM PIPES pH 6.4, 1 mM EDTA, 50° C. or 70° C.hybridization for 12-16 hours; followed by washing). Additionalpreferred hybridization conditions include hybridization at 70° C. in1×SSC or 50° C. in 1×SSC, 50% formamide followed by washing at 70° C. in0.3×SSC or hybridization at 70° C. in 4×SSC or 50° C. in 4×SSC, 50%formamide followed by washing at 67° C. in 1×SSC. The hybridizationtemperature for hybrids anticipated to be less than 50 base pairs inlength should be 5-10° C. less than the melting temperature (Tm) of thehybrid, where Tm is determined according to the following equations. Forhybrids less than 18 base pairs in length, Tm(° C.)=2(# of A+Tbases)+4(# of G+C bases). For hybrids between 18 and 49 base pairs inlength, Tm(° C.)=81.5+16.6(log 10[Na+])+0.41 (% G+C)−(600/N), where N isthe number of bases in the hybrid, and [Na+] is the concentration ofsodium ions in the hybridization buffer ([Na+] for 1×SSC=0.165 M).Additional examples of stringency conditions for polynucleotidehybridization are provided in Sambrook, J., E. F. Fritsch, and T.Maniatis, 1989, Molecular Cloning: A Laboratory Manual, Cold SpringHarbor Laboratory Press, Cold Spring Harbor, N.Y., chapters 9 and 11,and Current Protocols in Molecular Biology, 1995, F. M. Ausubel et al.,eds., John Wiley & Sons, Inc., sections 2.10 and 6.3-6.4. The length ofthe identical nucleotide sequences may be at least 10, 12, 15, 17, 20,22, 25, 27 or 30 bases.

By “conserved sequence region” is meant, a nucleotide sequence of one ormore regions in a polynucleotide does not vary significantly betweengenerations or from one biological system, subject, or organism toanother biological system, subject, or organism. The polynucleotide caninclude both coding and non-coding DNA and RNA.

By “sense region” is meant a nucleotide sequence of a dsRNA moleculehaving complementarity to an antisense region of the dsRNA molecule. Inaddition, the sense region of a dsRNA molecule can comprise a nucleicacid sequence having homology with a target nucleic acid sequence.

By “antisense region” is meant a nucleotide sequence of a dsRNA moleculehaving complementarity to a target nucleic acid sequence. In addition,the antisense region of a dsRNA molecule comprises a nucleic acidsequence having complementarity to a sense region of the dsRNA molecule.

As used herein, “antisense strand” refers to a single stranded nucleicacid molecule which has a sequence complementary to that of a targetRNA. When the antisense strand contains modified nucleotides with baseanalogs, it is not necessarily complementary over its entire length, butmust at least hybridize with a target RNA.

As used herein, “sense strand” refers to a single stranded nucleic acidmolecule which has a sequence complementary to that of an antisensestrand. When the antisense strand contains modified nucleotides withbase analogs, the sense strand need not be complementary over the entirelength of the antisense strand, but must at least duplex with theantisense strand.

As used herein, “guide strand” refers to a single stranded nucleic acidmolecule of a dsRNA or dsRNA-containing molecule, which has a sequencesufficiently complementary to that of a target RNA to result in RNAinterference. After cleavage of the dsRNA or dsRNA-containing moleculeby Dicer, a fragment of the guide strand remains associated with RISC,binds a target RNA as a component of the RISC complex, and promotescleavage of a target RNA by RISC. As used herein, the guide strand doesnot necessarily refer to a continuous single stranded nucleic acid andmay comprise a discontinuity, preferably at a site that is cleaved byDicer. A guide strand is an antisense strand.

As used herein, “passenger strand” refers to an oligonucleotide strandof a dsRNA or dsRNA-containing molecule, which has a sequence that iscomplementary to that of the guide strand. As used herein, the passengerstrand does not necessarily refer to a continuous single strandednucleic acid and may comprise a discontinuity, preferably at a site thatis cleaved by Dicer. A passenger strand is a sense strand.

By “target nucleic acid” is meant a nucleic acid sequence whoseexpression, level or activity is to be modulated. The target nucleicacid can be DNA or RNA. For agents that target MYC, in certainembodiments, the target nucleic acid is MYC RNA, e.g., in certainembodiments, MYC mRNA. MYC RNA target sites can also interchangeably bereferenced by corresponding cDNA sequences. Levels of MYC may also betargeted via targeting of upstream effectors of MYC, or the effects ofmodulated or misregulated MYC may also be modulated by targeting ofmolecules downstream of MYC in the MYC signalling pathway.

By “complementarity” is meant that a nucleic acid can form hydrogenbond(s) with another nucleic acid sequence by either traditionalWatson-Crick or other non-traditional types. In reference to the nucleicmolecules of the present invention, the binding free energy for anucleic acid molecule with its complementary sequence is sufficient toallow the relevant function of the nucleic acid to proceed, e.g., RNAiactivity. Determination of binding free energies for nucleic acidmolecules is well known in the art (see, e.g., Turner et al., 1987, CSHSymp. Quant. Biol. LII pp. 123-133; Frier et al., 1986, Proc. Nat. Acad.Sci. USA 83:9373-9377; Turner et al., 1987, J. Am. Chem. Soc.109:3783-3785). A percent complementarity indicates the percentage ofcontiguous residues in a nucleic acid molecule that can form hydrogenbonds (e.g., Watson-Crick base pairing) with a second nucleic acidsequence (e.g., 5, 6, 7, 8, 9, or 10 nucleotides out of a total of 10nucleotides in the first oligonucleotide being based paired to a secondnucleic acid sequence having 10 nucleotides represents 50%, 60%, 70%,80%, 90%, and 100% complementary respectively). “Perfectlycomplementary” means that all the contiguous residues of a nucleic acidsequence will hydrogen bond with the same number of contiguous residuesin a second nucleic acid sequence. In one embodiment, a dsRNA moleculeof the invention comprises 19 to 30 (e.g., 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, or 30 or more) nucleotides that are complementary to oneor more target nucleic acid molecules or a portion thereof.

In one embodiment, dsRNA molecules of the invention that down regulateor reduce MYC gene expression are used for treating, preventing orreducing MYC-related diseases or disorders (e.g., cancer) in a subjector organism.

In one embodiment of the present invention, each sequence of a DsiRNAmolecule of the invention is independently 25 to 35 nucleotides inlength, in specific embodiments 25, 26, 27, 28, 29, 30, 31, 32, 33, 34or 35 nucleotides in length. In another embodiment, the DsiRNA duplexesof the invention independently comprise 25 to 30 base pairs (e.g., 25,26, 27, 28, 29, or 30). In another embodiment, one or more strands ofthe DsiRNA molecule of the invention independently comprises 19 to 35nucleotides (e.g., 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,32, 33, 34 or 35) that are complementary to a target (MYC) nucleic acidmolecule. In certain embodiments, a DsiRNA molecule of the inventionpossesses a length of duplexed nucleotides between 25 and 34 nucleotidesin length (e.g., 25, 26, 27, 28, 29, 30, 31, 32, 33 or 34 nucleotides inlength; optionally, all such nucleotides base pair with cognatenucleotides of the opposite strand). (Exemplary DsiRNA molecules of theinvention are shown in FIG. 1, and below.

As used herein “cell” is used in its usual biological sense, and doesnot refer to an entire multicellular organism, e.g., specifically doesnot refer to a human. The cell can be present in an organism, e.g.,birds, plants and mammals such as humans, cows, sheep, apes, monkeys,swine, dogs, and cats. The cell can be prokaryotic (e.g., bacterialcell) or eukaryotic (e.g., mammalian or plant cell). The cell can be ofsomatic or germ line origin, totipotent or pluripotent, dividing ornon-dividing. The cell can also be derived from or can comprise a gameteor embryo, a stem cell, or a fully differentiated cell. Within certainaspects, the term “cell” refers specifically to mammalian cells, such ashuman cells, that contain one or more isolated dsRNA molecules of thepresent disclosure. In particular aspects, a cell processes dsRNAs ordsRNA-containing molecules resulting in RNA intereference of targetnucleic acids, and contains proteins and protein complexes required forRNAi, e.g., Dicer and RISC.

In certain embodiments, dsRNAs of the invention are Dicer substratesiRNAs (“DsiRNAs”). DsiRNAs can possess certain advantages as comparedto inhibitory nucleic acids that are not dicer substrates(“non-DsiRNAs”). Such advantages include, but are not limited to,enhanced duration of effect of a DsiRNA relative to a non-DsiRNA, aswell as enhanced inhibitory activity of a DsiRNA as compared to anon-DsiRNA (e.g., a 19-23mer siRNA) when each inhibitory nucleic acid issuitably formulated and assessed for inhibitory activity in a mammaliancell at the same concentration (in this latter scenario, the DsiRNAwould be identified as more potent than the non-DsiRNA). Detection ofthe enhanced potency of a DsiRNA relative to a non-DsiRNA is often mostreadily achieved at a formulated concentration (e.g., transfectionconcentration of the dsRNA) that results in the DsiRNA elicitingapproximately 30-70% knockdown activity upon a target RNA (e.g., amRNA). For active DsiRNAs, such levels of knockdown activity are mostoften achieved at in vitro mammalian cell DsiRNA transfectionconcentrations of 1 nM or less of as suitably formulated, and in certaininstances are observed at DsiRNA transfection concentrations of 200 pMor less, 100 pM or less, 50 pM or less, 20 pM or less, 10 pM or less, 5pM or less, or even 1 pM or less. Indeed, due to the variability amongDsiRNAs of the precise concentration at which 30-70% knockdown of atarget RNA is observed, construction of an IC₅₀ curve via assessment ofthe inhibitory activity of DsiRNAs and non-DsiRNAs across a range ofeffective concentrations is a preferred method for detecting theenhanced potency of a DsiRNA relative to a non-DsiRNA inhibitory agent.

In certain embodiments, a DsiRNA (in a state as initially formed, priorto dicer cleavage) is more potent at reducing MYC target gene expressionin a mammalian cell than a 19, 20, 21, 22 or 23 base pair sequence thatis contained within it. In certain such embodiments, a DsiRNA prior todicer cleavage is more potent than a 19-21mer contained within it.Optionally, a DsiRNA prior to dicer cleavage is more potent than a 19base pair duplex contained within it that is synthesized with symmetricdTdT overhangs (thereby forming a siRNA possessing 21 nucleotide strandlengths having dTdT overhangs). In certain embodiments, the DsiRNA ismore potent than a 19-23mer siRNA (e.g., a 19 base pair duplex with dTdToverhangs) that targets at least 19 nucleotides of the 21 nucleotidetarget sequence that is recited for a DsiRNA of the invention (withoutwishing to be bound by theory, the identity of a such a target site fora DsiRNA is identified via identification of the Ago2 cleavage site forthe DsiRNA; once the Ago2 cleavage site of a DsiRNA is determined for aDsiRNA, identification of the Ago2 cleavage site for any otherinhibitory dsRNA can be performed and these Ago2 cleavage sites can bealigned, thereby determining the alignment of projected targetnucleotide sequences for multiple dsRNAs). In certain relatedembodiments, the DsiRNA is more potent than a 19-23mer siRNA thattargets at least 20 nucleotides of the 21 nucleotide target sequencethat is recited for a DsiRNA of the invention. Optionally, the DsiRNA ismore potent than a 19-23mer siRNA that targets the same 21 nucleotidetarget sequence that is recited for a DsiRNA of the invention. Incertain embodiments, the DsiRNA is more potent than any 21mer siRNA thattargets the same 21 nucleotide target sequence that is recited for aDsiRNA of the invention. Optionally, the DsiRNA is more potent than any21 or 22mer siRNA that targets the same 21 nucleotide target sequencethat is recited for a DsiRNA of the invention. In certain embodiments,the DsiRNA is more potent than any 21, 22 or 23mer siRNA that targetsthe same 21 nucleotide target sequence that is recited for a DsiRNA ofthe invention. As noted above, such potency assessments are mosteffectively performed upon dsRNAs that are suitably formulated (e.g.,formulated with an appropriate transfection reagent) at a concentrationof 1 nM or less. Optionally, an IC₅₀ assessment is performed to evaluateactivity across a range of effective inhibitory concentrations, therebyallowing for robust comparison of the relative potencies of dsRNAs soassayed.

The dsRNA molecules of the invention are added directly, or can becomplexed with lipids (e.g., cationic lipids), packaged withinliposomes, or otherwise delivered to target cells or tissues. Thenucleic acid or nucleic acid complexes can be locally administered torelevant tissues ex vivo, or in vivo through direct dermal application,transdermal application, or injection, with or without theirincorporation in biopolymers. In particular embodiments, the nucleicacid molecules of the invention comprise sequences shown in FIG. 1, andthe below exemplary structures. Examples of such nucleic acid moleculesconsist essentially of sequences defined in these figures and exemplarystructures. Furthermore, where such agents are modified in accordancewith the below description of modification patterning of DsiRNA agents,chemically modified forms of constructs described in FIG. 1, and thebelow exemplary structures can be used in all uses described for theDsiRNA agents of FIG. 1, and the below exemplary structures.

In another aspect, the invention provides mammalian cells containing oneor more dsRNA molecules of this invention. The one or more dsRNAmolecules can independently be targeted to the same or different sites.

By “RNA” is meant a molecule comprising at least one, and preferably atleast 4, 8 and 12 ribonucleotide residues. The at least 4, 8 or 12 RNAresidues may be contiguous. By “ribonucleotide” is meant a nucleotidewith a hydroxyl group at the 2′ position of a 13-D-ribofuranose moiety.The terms include double-stranded RNA, single-stranded RNA, isolated RNAsuch as partially purified RNA, essentially pure RNA, synthetic RNA,recombinantly produced RNA, as well as altered RNA that differs fromnaturally occurring RNA by the addition, deletion, substitution and/oralteration of one or more nucleotides. Such alterations can includeaddition of non-nucleotide material, such as to the end(s) of the dsRNAor internally, for example at one or more nucleotides of the RNA.Nucleotides in the RNA molecules of the instant invention can alsocomprise non-standard nucleotides, such as non-naturally occurringnucleotides or chemically synthesized nucleotides or deoxynucleotides.These altered RNAs can be referred to as analogs or analogs ofnaturally-occurring RNA.

By “subject” is meant an organism, which is a donor or recipient ofexplanted cells or the cells themselves. “Subject” also refers to anorganism to which the dsRNA agents of the invention can be administered.A subject can be a mammal or mammalian cells, including a human or humancells.

The phrase “pharmaceutically acceptable carrier” refers to a carrier forthe administration of a therapeutic agent. Exemplary carriers includesaline, buffered saline, dextrose, water, glycerol, ethanol, andcombinations thereof. For drugs administered orally, pharmaceuticallyacceptable carriers include, but are not limited to pharmaceuticallyacceptable excipients such as inert diluents, disintegrating agents,binding agents, lubricating agents, sweetening agents, flavoring agents,coloring agents and preservatives. Suitable inert diluents includesodium and calcium carbonate, sodium and calcium phosphate, and lactose,while corn starch and alginic acid are suitable disintegrating agents.Binding agents may include starch and gelatin, while the lubricatingagent, if present, will generally be magnesium stearate, stearic acid ortalc. If desired, the tablets may be coated with a material such asglyceryl monostearate or glyceryl distearate, to delay absorption in thegastrointestinal tract. The pharmaceutically acceptable carrier of thedisclosed dsRNA compositions may be micellar structures, such as aliposomes, capsids, capsoids, polymeric nanocapsules, or polymericmicrocapsules.

Polymeric nanocapsules or microcapsules facilitate transport and releaseof the encapsulated or bound dsRNA into the cell. They include polymericand monomeric materials, especially including polybutylcyanoacrylate. Asummary of materials and fabrication methods has been published (seeKreuter, 1991). The polymeric materials which are formed from monomericand/or oligomeric precursors in the polymerization/nanoparticlegeneration step, are per se known from the prior art, as are themolecular weights and molecular weight distribution of the polymericmaterial which a person skilled in the field of manufacturingnanoparticles may suitably select in accordance with the usual skill.

Various methodologies of the instant invention include step thatinvolves comparing a value, level, feature, characteristic, property,etc. to a “suitable control”, referred to interchangeably herein as an“appropriate control”. A “suitable control” or “appropriate control” isa control or standard familiar to one of ordinary skill in the artuseful for comparison purposes. In one embodiment, a “suitable control”or “appropriate control” is a value, level, feature, characteristic,property, etc. determined prior to performing an RNAi methodology, asdescribed herein. For example, a transcription rate, mRNA level,translation rate, protein level, biological activity, cellularcharacteristic or property, genotype, phenotype, etc. can be determinedprior to introducing an RNA silencing agent (e.g., DsiRNA) of theinvention into a cell or organism. In another embodiment, a “suitablecontrol” or “appropriate control” is a value, level, feature,characteristic, property, etc. determined in a cell or organism, e.g., acontrol or normal cell or organism, exhibiting, for example, normaltraits. In yet another embodiment, a “suitable control” or “appropriatecontrol” is a predefined value, level, feature, characteristic,property, etc.

The term “in vitro” has its art recognized meaning, e.g., involvingpurified reagents or extracts, e.g., cell extracts. The term “in vivo”also has its art recognized meaning, e.g., involving living cells, e.g.,immortalized cells, primary cells, cell lines, and/or cells in anorganism.

“Treatment”, or “treating” as used herein, is defined as the applicationor administration of a therapeutic agent (e.g., a dsRNA agent or avector or transgene encoding same) to a patient, or application oradministration of a therapeutic agent to an isolated tissue or cell linefrom a patient, who has a disorder with the purpose to cure, heal,alleviate, relieve, alter, remedy, ameliorate, improve or affect thedisease or disorder, or symptoms of the disease or disorder. The term“treatment” or “treating” is also used herein in the context ofadministering agents prophylactically. The term “effective dose” or“effective dosage” is defined as an amount sufficient to achieve or atleast partially achieve the desired effect. The term “therapeuticallyeffective dose” is defined as an amount sufficient to cure or at leastpartially arrest the disease and its complications in a patient alreadysuffering from the disease. The term “patient” includes human and othermammalian subjects that receive either prophylactic or therapeutictreatment.

Structures of Anti-MYC DsiRNA Agents

In certain embodiments, the anti-MYC DsiRNA agents of the invention canhave the following structures:

In one such embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “Y” is an overhang domain comprised of 1-4 RNAmonomers that are optionally 2′-O-methyl RNA monomers. In a relatedembodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “Y” is an overhang domain comprised of 1-4 RNA monomersthat are optionally 2′-O-methyl RNA monomers, and “D”=DNA. In oneembodiment, the top strand is the sense strand, and the bottom strand isthe antisense strand. Alternatively, the bottom strand is the sensestrand and the top strand is the antisense strand.

DsiRNAs of the invention can carry a broad range of modificationpatterns (e.g., 2′-O-methyl RNA patterns, e.g., within extended DsiRNAagents). Certain modification patterns of the second strand of DsiRNAsof the invention are presented below.

In one embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. In arelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers, and“D”=DNA. The top strand is the sense strand, and the bottom strand isthe antisense strand.

In another such embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. In arelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand.

In another such embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. In arelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. In arelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. In a further relatedembodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M7” or “M7”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. In arelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. The top strand is the sense strand, and the bottomstrand is the antisense strand. In another related embodiment, theDsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M6” or “M6”modification pattern.

In other embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In a related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In anotherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M5” or “M5”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In a related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M4” or “M4”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In a related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M8” or “M8”modification pattern.

In other embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M3” or “M3”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In a related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M2” or “M2”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In a related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M1” or “M1”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M9” or “M9”modification pattern.

In other embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In a related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M10” or “M10”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M11” or “M11”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M12” or “M12”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M13” or “M13”modification pattern.

In other embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M21” or “M21”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M14” or “M14”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M15” or “M15”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In a related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M16” or “M16”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M17” or “M17”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M18” or “M18”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M19” or “M19”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M20” or “M20”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M22” or “M22”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M24” or “M24”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M25” or “M25”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M26” or “M26”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M27” or “M27”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M28” or “M28”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M29” or “M29”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M30” or “M30”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M31” or “M31”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M32” or “M32”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M34” or “M34”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M35” or “M35”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M37” or “M37”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M38” or “M38”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M40” or “M40”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M41” or “M41”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M36” or “M36”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M42” or “M42”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M43” or “M43”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M44” or “M44”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M45” or “M45”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M46” or “M46”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M47” or “M47”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M48” or “M48”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M52” or “M52”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M54” or “M54”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M55” or “M55”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M56” or “M56”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M57” or “M57”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M58” or “M58”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M59” or “M59”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M60” or “M60”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M61” or “M61”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M62” or “M62”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M63” or “M63”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M64” or “M64”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M65” or “M65”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M66” or “M66”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M67” or “M67”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M68” or “M68”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M69” or “M69”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M70” or “M70”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M71” or “M71”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M72” or “M72”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers and underlined residues are 2′-O-methyl RNA monomers. The topstrand is the sense strand, and the bottom strand is the antisensestrand. In one related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M73” or “M73”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. In a further relatedembodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M7*” or “M7*”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M6*” or “M6*”modification pattern.

In other embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In anotherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M5*” or “M5*”modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M4*” or “M4*”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M8*” or “M8*”modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M2*” or “M2*”modification pattern.

In other embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M10*” or“M10*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M11*” or“M11*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M13*” or“M13*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M14*” or“M14*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M15*” or“M15*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M16*” or“M16*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M17*” or“M17*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M18*” or“M18*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M19*” or“M19*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-YXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an overhang domaincomprised of 1-4 RNA monomers that are optionally 2′-O-methyl RNAmonomers, underlined residues are 2′-O-methyl RNA monomers, and “D”=DNA.The top strand is the sense strand, and the bottom strand is theantisense strand. In another related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M20*” or“M20*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M22*” or“M22*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M24*” or“M24*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M25*” or“M25*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M26*” or“M26*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M27*” or“M27*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M28*” or“M28*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M29*” or“M29*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M34*” or“M34*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M35*” or“M35*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M37*” or“M37*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M38*” or“M38*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M40*” or“M40*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M41*” or“M41*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M36*” or“M36*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M42*” or“M42*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M43*” or“M43*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M44*” or“M44*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M46*” or“M46*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M47*” or“M47*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M48*” or“M48*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M52*” or“M52*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M54*” or“M54*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M55*” or“M55*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M56*” or“M56*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M57*” or“M57*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M58*” or“M58*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M59*” or“M59*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M60*” or“M60*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M61*” or“M61*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M62*” or“M62*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M63*” or“M63*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M64*” or“M64*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M65*” or“M65*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M66*” or“M66*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M67*” or“M67*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M68*” or“M68*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M69*” or“M69*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M70*” or“M70*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M71*” or“M71*” modification pattern.

In further embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M72*” or“M72*” modification pattern.

In additional embodiments, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA and “X”=2′-O-methyl RNA. The top strand is the sensestrand, and the bottom strand is the antisense strand. In a furtherrelated embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, and “D”=DNA. The top strand is thesense strand, and the bottom strand is the antisense strand. Thismodification pattern is also referred to herein as the “AS-M73*” or“M73*” modification pattern.

In certain embodiments, the sense strand of a DsiRNA of the invention ismodified—specific exemplary forms of sense strand modifications areshown below, and it is contemplated that such modified sense strands canbe substituted for the sense strand of any of the DsiRNAs shown above togenerate a DsiRNA comprising a below-depicted sense strand that annealswith an above-depicted antisense strand. Exemplary sense strandmodification patterns include:

5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM1” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM2” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM3”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM4” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM5” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM6”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM7” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM8” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM9”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM10” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM11” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM12”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM13” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM14” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM15”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM16” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM17” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM18”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM19” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM20” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM21”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM23” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM24” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM25”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM30” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM31” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM32”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM33” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM34” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM35”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM36” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM37” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM38”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM39” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM40” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM41”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM42” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM43” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM44”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM45”, “SM47”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM46” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM48” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM49”5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM50” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′“SM51” 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′ “SM52”5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ 5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′5′-XXXXXXXXXXXXXXXXXXXXXXXXX-3′ “SM22” where “X” = RNA,“X” = 2′-O-methyl RNA, and “D” = DNA.

The above modification patterns can also be incorporated into, e.g., theextended DsiRNA structures and mismatch and/or frayed DsiRNA structuresdescribed below.

In another embodiment, the DsiRNA comprises strands having equal lengthspossessing 1-3 mismatched residues that serve to orient Dicer cleavage(specifically, one or more of positions 1, 2 or 3 on the first strand ofthe DsiRNA, when numbering from the 3′-terminal residue, are mismatchedwith corresponding residues of the 5′-terminal region on the secondstrand when first and second strands are annealed to one another). Anexemplary 27mer DsiRNA agent with two terminal mismatched residues isshown:

wherein “X”=RNA, “M”=Nucleic acid residues (RNA, DNA or non-natural ormodified nucleic acids) that do not base pair (hydrogen bond) withcorresponding “M” residues of otherwise complementary strand whenstrands are annealed. Any of the residues of such agents can optionallybe 2′-O-methyl RNA monomers—alternating positioning of 2′-O-methyl RNAmonomers that commences from the 3′-terminal residue of the bottom(second) strand, as shown for above asymmetric agents, can also be usedin the above “blunt/fray” DsiRNA agent. In one embodiment, the topstrand is the sense strand, and the bottom strand is the antisensestrand. Alternatively, the bottom strand is the sense strand and the topstrand is the antisense strand.

In certain additional embodiments, the present invention providescompositions for RNA interference (RNAi) that possess one or more basepaired deoxyribonucleotides within a region of a double strandedribonucleic acid (dsRNA) that is positioned 3′ of a projected sensestrand Dicer cleavage site and correspondingly 5′ of a projectedantisense strand Dicer cleavage site. The compositions of the inventioncomprise a dsRNA which is a precursor molecule, i.e., the dsRNA of thepresent invention is processed in vivo to produce an active smallinterfering nucleic acid (siRNA). The dsRNA is processed by Dicer to anactive siRNA which is incorporated into RISC.

In certain embodiments, the DsiRNA agents of the invention can have thefollowing exemplary structures (noting that any of the followingexemplary structures can be combined, e.g., with the bottom strandmodification patterns of the above-described structures—in one specificexample, the bottom strand modification pattern shown in any of theabove structures is applied to the 27 most 3′ residues of the bottomstrand of any of the following structures; in another specific example,the bottom strand modification pattern shown in any of the abovestructures upon the 23 most 3′ residues of the bottom strand is appliedto the 23 most 3′ residues of the bottom strand of any of the followingstructures):

In one such embodiment, the DsiRNA comprises the following (an exemplary“right-extended”, “DNA extended” DsiRNA):

5′-XXXXXXXXXXXXXXXXXXXXXXXX_(N)*D_(N)DD-3′3′-YXXXXXXXXXXXXXXXXXXXXXXXX_(N)*D_(N)XX-5′wherein “X”=RNA, “Y” is an optional overhang domain comprised of 0-10RNA monomers that are optionally 2′-O-methyl RNA monomers—in certainembodiments, “Y” is an overhang domain comprised of 1-4 RNA monomersthat are optionally 2′-O-methyl RNA monomers, “D”=DNA, and “N”=1 to 50or more, but is optionally 1-8 or 1-10. “N*”=0 to 15 or more, but isoptionally 0, 1, 2, 3, 4, 5 or 6. In one embodiment, the top strand isthe sense strand, and the bottom strand is the antisense strand.Alternatively, the bottom strand is the sense strand and the top strandis the antisense strand.

In a related embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXX_(N)*D_(N)DD-3′3′-YXXXXXXXXXXXXXXXXXXXXXXXX_(N)*D_(N)DD-5′wherein “X”=RNA, “Y” is an optional overhang domain comprised of 0-10RNA monomers that are optionally 2′-O-methyl RNA monomers—in certainembodiments, “Y” is an overhang domain comprised of 1-4 RNA monomersthat are optionally 2′-O-methyl RNA monomers, “D”=DNA, and “N”=1 to 50or more, but is optionally 1-8 or 1-10. “N*”=0 to 15 or more, but isoptionally 0, 1, 2, 3, 4, 5 or 6. In one embodiment, the top strand isthe sense strand, and the bottom strand is the antisense strand.Alternatively, the bottom strand is the sense strand and the top strandis the antisense strand.

In an additional embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXX_(N*)D_(N)DD-3′3′-YXXXXXXXXXXXXXXXXXXXXXXXX_(N*)D_(N)ZZ-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an optional overhang domaincomprised of 0-10 RNA monomers that are optionally 2′-O-methyl RNAmonomers—in certain embodiments, “Y” is an overhang domain comprised of1-4 RNA monomers that are optionally 2′-O-methyl RNA monomers, “D”=DNA,“Z”=DNA or RNA, and “N”=1 to 50 or more, but is optionally 1-8 or 1-10.“N*”=0 to 15 or more, but is optionally 0, 1, 2, 3, 4, 5 or 6. In oneembodiment, the top strand is the sense strand, and the bottom strand isthe antisense strand. Alternatively, the bottom strand is the sensestrand and the top strand is the antisense strand, with 2′-O-methyl RNAmonomers located at alternating residues along the top strand, ratherthan the bottom strand presently depicted in the above schematic.

In another such embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXX_(N*)D_(N)DD-3′3′-YXXXXXXXXXXXXXXXXXXXXXXXX_(N*)D_(N)ZZ-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an optional overhang domaincomprised of 0-10 RNA monomers that are optionally 2′-O-methyl RNAmonomers—in certain embodiments, “Y” is an overhang domain comprised of1-4 RNA monomers that are optionally 2′-O-methyl RNA monomers, “D”=DNA,“Z”=DNA or RNA, and “N”=1 to 50 or more, but is optionally 1-8 or 1-10.“N*”=0 to 15 or more, but is optionally 0, 1, 2, 3, 4, 5 or 6. In oneembodiment, the top strand is the sense strand, and the bottom strand isthe antisense strand. Alternatively, the bottom strand is the sensestrand and the top strand is the antisense strand, with 2′-O-methyl RNAmonomers located at alternating residues along the top strand, ratherthan the bottom strand presently depicted in the above schematic.

In another such embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXX_(N*)D_(N)DD-3′3′-YXXXXXXXXXXXXXXXXXXXXXXXX_(N*)D_(N)ZZ-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “Y” is an optional overhang domaincomprised of 0-10 RNA monomers that are optionally 2′-O-methyl RNAmonomers—in certain embodiments, “Y” is an overhang domain comprised of1-4 RNA monomers that are optionally 2′-O-methyl RNA monomers, “D”=DNA,“Z”=DNA or RNA, and “N”=1 to 50 or more, but is optionally 1-8 or 1-10.“N*”=0 to 15 or more, but is optionally 0, 1, 2, 3, 4, 5 or 6. In oneembodiment, the top strand is the sense strand, and the bottom strand isthe antisense strand. Alternatively, the bottom strand is the sensestrand and the top strand is the antisense strand, with 2′-O-methyl RNAmonomers located at alternating residues along the top strand, ratherthan the bottom strand presently depicted in the above schematic.

In another embodiment, the DsiRNA comprises:

5′-XXXXXXXXXXXXXXXXXXXXXXXX_(N*)[X1/D1]_(N)DD-3′3′-YXXXXXXXXXXXXXXXXXXXXXXXX_(N*)[X2/D2]_(N)ZZ-5′wherein “X”=RNA, “Y” is an optional overhang domain comprised of 0-10RNA monomers that are optionally 2′-O-methyl RNA monomers—in certainembodiments, “Y” is an overhang domain comprised of 1-4 RNA monomersthat are optionally 2′-O-methyl RNA monomers, “D”=DNA, “Z”=DNA or RNA,and “N”=1 to 50 or more, but is optionally 1-8 or 1-10, where at leastone D1_(N) is present in the top strand and is base paired with acorresponding D2_(N) in the bottom strand. Optionally, D1_(N) andD1_(N+1) are base paired with corresponding D2_(N) and D2_(N+1); D1_(N),D1_(N+1) and D1_(N+2) are base paired with corresponding D2_(N),D1_(N+1) and D1_(N+2), etc. “N*”=0 to 15 or more, but is optionally 0,1, 2, 3, 4, 5 or 6. In one embodiment, the top strand is the sensestrand, and the bottom strand is the antisense strand. Alternatively,the bottom strand is the sense strand and the top strand is theantisense strand, with 2′-O-methyl RNA monomers located at alternatingresidues along the top strand, rather than the bottom strand presentlydepicted in the above schematic.

In the structures depicted herein, the 5′ end of either the sense strandor antisense strand can optionally comprise a phosphate group.

In another embodiment, a DNA:DNA-extended DsiRNA comprises strandshaving equal lengths possessing 1-3 mismatched residues that serve toorient Dicer cleavage (specifically, one or more of positions 1, 2 or 3on the first strand of the DsiRNA, when numbering from the 3′-terminalresidue, are mismatched with corresponding residues of the 5′-terminalregion on the second strand when first and second strands are annealedto one another). An exemplary DNA:DNA-extended DsiRNA agent with twoterminal mismatched residues is shown:

wherein “X”=RNA, “M”=Nucleic acid residues (RNA, DNA or non-natural ormodified nucleic acids) that do not base pair (hydrogen bond) withcorresponding “M” residues of otherwise complementary strand whenstrands are annealed, “D”=DNA and “N”=1 to 50 or more, but is optionally1-15 or, optionally, 1-8. “N*”=0 to 15 or more, but is optionally 0, 1,2, 3, 4, 5 or 6. Any of the residues of such agents can optionally be2′-O-methyl RNA monomers—alternating positioning of 2′-O-methyl RNAmonomers that commences from the 3′-terminal residue of the bottom(second) strand, as shown for above asymmetric agents, can also be usedin the above “blunt/fray” DsiRNA agent. In one embodiment, the topstrand (first strand) is the sense strand, and the bottom strand (secondstrand) is the antisense strand. Alternatively, the bottom strand is thesense strand and the top strand is the antisense strand. Modificationand DNA:DNA extension patterns paralleling those shown above forasymmetric/overhang agents can also be incorporated into such“blunt/frayed” agents.

In one embodiment, a length-extended DsiRNA agent is provided thatcomprises deoxyribonucleotides positioned at sites modeled to functionvia specific direction of Dicer cleavage, yet which does not require thepresence of a base-paired deoxyribonucleotide in the dsRNA structure. Anexemplary structure for such a molecule is shown:

5′-XXXXXXXXXXXXXXXXXXXDDXX-3′ 3′-YXXXXXXXXXXXXXXXXXDDXXXX-5′wherein “X”=RNA, “Y” is an optional overhang domain comprised of 0-10RNA monomers that are optionally 2′-O-methyl RNA monomers—in certainembodiments, “Y” is an overhang domain comprised of 1-4 RNA monomersthat are optionally 2′-O-methyl RNA monomers, and “D”=DNA. In oneembodiment, the top strand is the sense strand, and the bottom strand isthe antisense strand. Alternatively, the bottom strand is the sensestrand and the top strand is the antisense strand. The above structureis modeled to force Dicer to cleave a minimum of a 21mer duplex as itsprimary post-processing form. In embodiments where the bottom strand ofthe above structure is the antisense strand, the positioning of twodeoxyribonucleotide residues at the ultimate and penultimate residues ofthe 5′ end of the antisense strand will help reduce off-target effects(as prior studies have shown a 2′-O-methyl modification of at least thepenultimate position from the 5′ terminus of the antisense strand toreduce off-target effects; see, e.g., US 2007/0223427).

In one embodiment, the DsiRNA comprises the following (an exemplary“left-extended”, “DNA extended” DsiRNA):

5′-D_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)Y-3′3′-D_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)-5′wherein “X”=RNA, “Y” is an optional overhang domain comprised of 0-10RNA monomers that are optionally 2′-O-methyl RNA monomers—in certainembodiments, “Y” is an overhang domain comprised of 1-4 RNA monomersthat are optionally 2′-O-methyl RNA monomers, “D”=DNA, and “N”=1 to 50or more, but is optionally 1-8 or 1-10. “N*”=0 to 15 or more, but isoptionally 0, 1, 2, 3, 4, 5 or 6. In one embodiment, the top strand isthe sense strand, and the bottom strand is the antisense strand.Alternatively, the bottom strand is the sense strand and the top strandis the antisense strand.

In a related embodiment, the DsiRNA comprises:

5′-D_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)DD-3′3′-D_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)XX-5′wherein “X”=RNA, optionally a 2′-O-methyl RNA monomers “D”=DNA, “N”=1 to50 or more, but is optionally 1-8 or 1-10. “N*”=0 to 15 or more, but isoptionally 0, 1, 2, 3, 4, 5 or 6. In one embodiment, the top strand isthe sense strand, and the bottom strand is the antisense strand.Alternatively, the bottom strand is the sense strand and the top strandis the antisense strand.

In an additional embodiment, the DsiRNA comprises:

5′-D_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)DD-3′ 3′-D_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)ZZ-5′wherein “X”=RNA, optionally a 2′-O-methyl RNA monomers “D”=DNA, “N”=1 to50 or more, but is optionally 1-8 or 1-10. “N*”=0 to 15 or more, but isoptionally 0, 1, 2, 3, 4, 5 or 6. “Z”=DNA or RNA. In one embodiment, thetop strand is the sense strand, and the bottom strand is the antisensestrand. Alternatively, the bottom strand is the sense strand and the topstrand is the antisense strand, with 2′-O-methyl RNA monomers located atalternating residues along the top strand, rather than the bottom strandpresently depicted in the above schematic.

In another such embodiment, the DsiRNA comprises:

5′-D_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)DD-3′ 3′-D_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)ZZ-5′wherein “X”=RNA, optionally a 2′-O-methyl RNA monomers “D”=DNA, “N”=1 to50 or more, but is optionally 1-8 or 1-10. “N*”=0 to 15 or more, but isoptionally 0, 1, 2, 3, 4, 5 or 6. “Z”=DNA or RNA. In one embodiment, thetop strand is the sense strand, and the bottom strand is the antisensestrand. Alternatively, the bottom strand is the sense strand and the topstrand is the antisense strand, with 2′-O-methyl RNA monomers located atalternating residues along the top strand, rather than the bottom strandpresently depicted in the above schematic.

In another such embodiment, the DsiRNA comprises:

5′-D_(N)ZZXXXXXXXXXXXXXXXXXXXXXXXX_(N*)DD-3′ 3′-D_(N)XXXXXXXXXXXXXXXXXXXXXXXXXX_(N*)ZZ-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “D”=DNA, “Z”=DNA or RNA, and “N”=1to 50 or more, but is optionally 1-8 or 1-10. “N*”=0 to 15 or more, butis optionally 0, 1, 2, 3, 4, 5 or 6. In one embodiment, the top strandis the sense strand, and the bottom strand is the antisense strand.Alternatively, the bottom strand is the sense strand and the top strandis the antisense strand, with 2′-O-methyl RNA monomers located atalternating residues along the top strand, rather than the bottom strandpresently depicted in the above schematic.

In another such embodiment, the DsiRNA comprises:

5′-D_(N)ZZXXXXXXXXXXXXXXXXXXXXXXXX_(N*)Y-3′ 3′-D_(N)XXXXXXXXXXXXXXXXXXXXXXXXXX_(N*)-5′wherein “X”=RNA, “X”=2′-O-methyl RNA, “D”=DNA, “Z”=DNA or RNA, and “N”=1to 50 or more, but is optionally 1-8 or 1-10. “N*”=0 to 15 or more, butis optionally 0, 1, 2, 3, 4, 5 or 6. “Y” is an optional overhang domaincomprised of 0-10 RNA monomers that are optionally 2′-O-methyl RNAmonomers—in certain embodiments, “Y” is an overhang domain comprised of1-4 RNA monomers that are optionally 2′-O-methyl RNA monomers. In oneembodiment, the top strand is the sense strand, and the bottom strand isthe antisense strand. Alternatively, the bottom strand is the sensestrand and the top strand is the antisense strand, with 2′-O-methyl RNAmonomers located at alternating residues along the top strand, ratherthan the bottom strand presently depicted in the above schematic.

In another embodiment, the DsiRNA comprises:

5′-[X1/D1]_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)DD-3′3′-[X2/D2]_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)ZZ-5′wherein “X”=RNA, “D”=DNA, “Z”=DNA or RNA, and “N”=1 to 50 or more, butis optionally 1-8 or 1-10, where at least one D1_(N) is present in thetop strand and is base paired with a corresponding D2_(N) in the bottomstrand. Optionally, D1_(N) and D1_(N+1) are base paired withcorresponding D2_(N) and D2_(N+1); D1_(N), D1_(N+1) and D1_(N+2) arebase paired with corresponding D2_(N), D1_(N+1) and D1_(N+2), etc.“N*”=0 to 15 or more, but is optionally 0, 1, 2, 3, 4, 5 or 6. In oneembodiment, the top strand is the sense strand, and the bottom strand isthe antisense strand. Alternatively, the bottom strand is the sensestrand and the top strand is the antisense strand, with 2′-O-methyl RNAmonomers located at alternating residues along the top strand, ratherthan the bottom strand presently depicted in the above schematic.

In a related embodiment, the DsiRNA comprises:

5′-[X1/D1]_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)Y-3′3′-[X2/D2]_(N)XXXXXXXXXXXXXXXXXXXXXXXX_(N*)-5′wherein “X”=RNA, “D”=DNA, “Y” is an optional overhang domain comprisedof 0-10 RNA monomers that are optionally 2′-O-methyl RNA monomers—incertain embodiments, “Y” is an overhang domain comprised of 1-4 RNAmonomers that are optionally 2′-O-methyl RNA monomers, and “N”=1 to 50or more, but is optionally 1-8 or 1-10, where at least one D1_(N) ispresent in the top strand and is base paired with a corresponding D2_(N)in the bottom strand. Optionally, D1_(x) and D1_(N+1) are base pairedwith corresponding D2_(N) and D2_(N+1); D1_(x), D1_(N+1) and D1_(N+2)are base paired with corresponding D2_(N), D1_(N+1) and D1_(N+2), etc.“N*”=0 to 15 or more, but is optionally 0, 1, 2, 3, 4, 5 or 6. In oneembodiment, the top strand is the sense strand, and the bottom strand isthe antisense strand. Alternatively, the bottom strand is the sensestrand and the top strand is the antisense strand, with 2′-O-methyl RNAmonomers located at alternating residues along the top strand, ratherthan the bottom strand presently depicted in the above schematic.

In another embodiment, the DNA:DNA-extended DsiRNA comprises strandshaving equal lengths possessing 1-3 mismatched residues that serve toorient Dicer cleavage (specifically, one or more of positions 1, 2 or 3on the first strand of the DsiRNA, when numbering from the 3′-terminalresidue, are mismatched with corresponding residues of the 5′-terminalregion on the second strand when first and second strands are annealedto one another). An exemplary DNA:DNA-extended DsiRNA agent with twoterminal mismatched residues is shown:

wherein “X”=RNA, “M”=Nucleic acid residues (RNA, DNA or non-natural ormodified nucleic acids) that do not base pair (hydrogen bond) withcorresponding “M” residues of otherwise complementary strand whenstrands are annealed, “D”=DNA and “N”=1 to 50 or more, but is optionally1-8 or 1-10. “N*”=0 to 15 or more, but is optionally 0, 1, 2, 3, 4, 5 or6. Any of the residues of such agents can optionally be 2′-O-methyl RNAmonomers—alternating positioning of 2′-O-methyl RNA monomers thatcommences from the 3′-terminal residue of the bottom (second) strand, asshown for above asymmetric agents, can also be used in the above“blunt/fray” DsiRNA agent. In one embodiment, the top strand (firststrand) is the sense strand, and the bottom strand (second strand) isthe antisense strand. Alternatively, the bottom strand is the sensestrand and the top strand is the antisense strand. Modification andDNA:DNA extension patterns paralleling those shown above forasymmetric/overhang agents can also be incorporated into such“blunt/frayed” agents.

In another embodiment, a length-extended DsiRNA agent is provided thatcomprises deoxyribonucleotides positioned at sites modeled to functionvia specific direction of Dicer cleavage, yet which does not require thepresence of a base-paired deoxyribonucleotide in the dsRNA structure.Exemplary structures for such a molecule are shown:

5′-XXDDXXXXXXXXXXXXXXXXXXXX_(N*)Y-3′ 3′-DDXXXXXXXXXXXXXXXXXXXXXX_(N*)-5′or 5′-XDXDXXXXXXXXXXXXXXXXXXXX_(N*)Y-3′3′-DXDXXXXXXXXXXXXXXXXXXXXX_(N*)-5′wherein “X”=RNA, “Y” is an optional overhang domain comprised of 0-10RNA monomers that are optionally 2′-O-methyl RNA monomers—in certainembodiments, “Y” is an overhang domain comprised of 1-4 RNA monomersthat are optionally 2′-O-methyl RNA monomers, and “D”=DNA. “N*”=0 to 15or more, but is optionally 0, 1, 2, 3, 4, 5 or 6. In one embodiment, thetop strand is the sense strand, and the bottom strand is the antisensestrand. Alternatively, the bottom strand is the sense strand and the topstrand is the antisense strand.

In any of the above embodiments where the bottom strand of the abovestructure is the antisense strand, the positioning of twodeoxyribonucleotide residues at the ultimate and penultimate residues ofthe 5′ end of the antisense strand will help reduce off-target effects(as prior studies have shown a 2′-O-methyl modification of at least thepenultimate position from the 5′ terminus of the antisense strand toreduce off-target effects; see, e.g., US 2007/0223427).

In certain embodiments, the “D” residues of the above structures includeat least one PS-DNA or PS-RNA. Optionally, the “D” residues of the abovestructures include at least one modified nucleotide that inhibits Dicercleavage.

While the above-described “DNA-extended” DsiRNA agents can becategorized as either “left extended” or “right extended”, DsiRNA agentscomprising both left- and right-extended DNA-containing sequences withina single agent (e.g., both flanks surrounding a core dsRNA structure aredsDNA extensions) can also be generated and used in similar manner tothose described herein for “right-extended” and “left-extended” agents.

In some embodiments, the DsiRNA of the instant invention furthercomprises a linking moiety or domain that joins the sense and antisensestrands of a DNA:DNA-extended DsiRNA agent. Optionally, such a linkingmoiety domain joins the 3′ end of the sense strand and the 5′ end of theantisense strand. The linking moiety may be a chemical (non-nucleotide)linker, such as an oligomethylenediol linker, oligoethylene glycollinker, or other art-recognized linker moiety. Alternatively, the linkercan be a nucleotide linker, optionally including an extended loop and/ortetraloop.

In one embodiment, the DsiRNA agent has an asymmetric structure, withthe sense strand having a 25-base pair length, and the antisense strandhaving a 27-base pair length with a 1-4 base 3′-overhang (e.g., a onebase 3′-overhang, a two base 3′-overhang, a three base 3′-overhang or afour base 3′-overhang). In another embodiment, this DsiRNA agent has anasymmetric structure further containing 2 deoxynucleotides at the 3′ endof the sense strand.

In another embodiment, the DsiRNA agent has an asymmetric structure,with the antisense strand having a 25-base pair length, and the sensestrand having a 27-base pair length with a 1-4 base 3′-overhang (e.g., aone base 3′-overhang, a two base 3′-overhang, a three base 3′-overhangor a four base 3′-overhang). In another embodiment, this DsiRNA agenthas an asymmetric structure further containing 2 deoxyribonucleotides atthe 3′ end of the antisense strand.

Exemplary MYC targeting DsiRNA agents of the invention, and theirassociated MYC target sequences, include the following, presented in thebelow series of tables:

Table Number:

(2) Selected Human Anti-MYC DsiRNA Agents (Asymmetrics);

(3) Selected Human Anti-MYC DsiRNAs, Unmodified Duplexes (Asymmetrics);

(4) Selected Mouse Anti-MYC DsiRNAs (Asymmetrics);

(5) DsiRNA Target Sequences (21mers) In MYC mRNA;

(6) Selected Human Anti-MYC “Blunt/Fray” DsiRNAs;

(7) Selected Human Anti-MYC “Blunt/Blunt” DsiRNAs; and

(8) DsiRNA Component 19 Nucleotide Target Sequences In MYC mRNA

TABLE 2 Selected Human Anti-MYC DsiRNA Agents (Asymmetrics)5′-CGAGAAGGGCAGGGCUUCUCAGAgg-3′ (SEQ ID NO: 1)3′-GAGCUCUUCCCGUCCCGAAGAGUCUCC-5′ (SEQ ID NO: 328) MYC-94 Target:5′-CTCGAGAAGGGCAGGGCTTCTCAGAGG-3′ (SEQ ID NO: 655)5′-GCUUUAUCUAACUCGCUGUAGUAat-3′ (SEQ ID NO: 2)3′-CCCGAAAUAGAUUGAGCGACAUCAUUA-5′ (SEQ ID NO: 329) MYC-178 Target:5′-GGGCTTTATCTAACTCGCTGTAGTAAT-3′ (SEQ ID NO: 656)5′-CCCUUGCCGCAUCCACGAAACUUtg-3′ (SEQ ID NO: 3)3′-UUGGGAACGGCGUAGGUGCUUUGAAAC-5′ (SEQ ID NO: 330) MYC-365 Target:5′-AACCCTTGCCGCATCCACGAAACTTTG-3′ (SEQ ID NO: 657)5′-GCCGCAUCCACGAAACUUUGCCCat-3′ (SEQ ID NO: 4)3′-AACGGCGUAGGUGCUUUGAAACGGGUA-5′ (SEQ ID NO: 331) MYC-370 Target:5′-TTGCCGCATCCACGAAACTTTGCCCAT-3′ (SEQ ID NO: 658)5′-UCCACGAAACUUUGCCCAUAGCAgc-3′ (SEQ ID NO: 5)3′-GUAGGUGCUUUGAAACGGGUAUCGUCG-5′ (SEQ ID NO: 332) MYC-376 Target:5′-CATCCACGAAACTTTGCCCATAGCAGC-3′ (SEQ ID NO: 659)5′-GCGGGCACUUUGCACUGGAACUUac-3′ (SEQ ID NO: 6)3′-CCCGCCCGUGAAACGUGACCUUGAAUG-5′ (SEQ ID NO: 333) MYC-403 Target:5′-GGGCGGGCACTTTGCACTGGAACTTAC-3′ (SEQ ID NO: 660)5′-ACUUUGCACUGGAACUUACAACAcc-3′ (SEQ ID NO: 7)3′-CGUGAAACGUGACCUUGAAUGUUGUGG-5′ (SEQ ID NO: 334) MYC-409 Target:5′-GCACTTTGCACTGGAACTTACAACACC-3′ (SEQ ID NO: 661)5′-CUGGAACUUACAACACCCGAGCAag-3′ (SEQ ID NO: 8)3′-GUGACCUUGAAUGUUGUGGGCUCGUUC-5′ (SEQ ID NO: 335) MYC-417 Target:5′-CACTGGAACTTACAACACCCGAGCAAG-3′ (SEQ ID NO: 662)5′-GCAGCUGCUUAGACGCUGGAUUUtt-3′ (SEQ ID NO: 9)3′-AACGUCGACGAAUCUGCGACCUAAAAA-5′ (SEQ ID NO: 336) MYC-535 Target:5′-TTGCAGCTGCTTAGACGCTGGATTTTT-3′ (SEQ ID NO: 663)5′-GCUUAGACGCUGGAUUUUUUUCGgg-3′ (SEQ ID NO: 10)3′-GACGAAUCUGCGACCUAAAAAAAGCCC-5′ (SEQ ID NO: 337) MYC-541 Target:5′-CTGCTTAGACGCTGGATTTTTTTCGGG-3′ (SEQ ID NO: 664)5′-CGCUGGAUUUUUUUCGGGUAGUGga-3′ (SEQ ID NO: 11)3′-CUGCGACCUAAAAAAAGCCCAUCACCU-5′ (SEQ ID NO: 338) MYC-548 Target:5′-GACGCTGGATTTTTTTCGGGTAGTGGA-3′ (SEQ ID NO: 665)5′-GAUUUUUUUCGGGUAGUGGAAAAcc-3′ (SEQ ID NO: 12)3′-ACCUAAAAAAAGCCCAUCACCUUUUGG-5′ (SEQ ID NO: 339) MYC-553 Target:5′-TGGATTTTTTTCGGGTAGTGGAAAACC-3′ (SEQ ID NO: 666)5′-CGGGUAGUGGAAAACCAGCAGCCtc-3′ (SEQ ID NO: 13)3′-AAGCCCAUCACCUUUUGGUCGUCGGAG-5′ (SEQ ID NO: 340) MYC-562 Target:5′-TTCGGGTAGTGGAAAACCAGCAGCCTC-3′ (SEQ ID NO: 667)5′-CUCAACGUUAGCUUCACCAACAGga-3′ (SEQ ID NO: 14)3′-GGGAGUUGCAAUCGAAGUGGUUGUCCU-5′ (SEQ ID NO: 341) MYC-601 Target:5′-CCCTCAACGTTAGCTTCACCAACAGGA-3′ (SEQ ID NO: 668)5′-GUUAGCUUCACCAACAGGAACUAtg-3′ (SEQ ID NO: 15)3′-UGCAAUCGAAGUGGUUGUCCUUGAUAC-5′ (SEQ ID NO: 342) MYC-607 Target:5′-ACGTTAGCTTCACCAACAGGAACTATG-3′ (SEQ ID NO: 669)5′-GACUCGGUGCAGCCGUAUUUCUAct-3′ (SEQ ID NO: 16)3′-UGCUGAGCCACGUCGGCAUAAAGAUGA-5′ (SEQ ID NO: 343) MYC-643 Target:5′-ACGACTCGGTGCAGCCGTATTTCTACT-3′ (SEQ ID NO: 670)5′-GCAGCCGUAUUUCUACUGCGACGag-3′ (SEQ ID NO: 17)3′-CACGUCGGCAUAAAGAUGACGCUGCUC-5′ (SEQ ID NO: 344) MYC-651 Target:5′-GTGCAGCCGTATTTCTACTGCGACGAG-3′ (SEQ ID NO: 671)5′-GAGGAGAACUUCUACCAGCAGCAgc-3′ (SEQ ID NO: 18)3′-UCCUCCUCUUGAAGAUGGUCGUCGUCG-5′ (SEQ ID NO: 345) MYC-676 Target:5′-AGGAGGAGAACTTCTACCAGCAGCAGC-3′ (SEQ ID NO: 672)5′-GCGAGGAUAUCUGGAAGAAAUUCga-3′ (SEQ ID NO: 19)3′-GUCGCUCCUAUAGACCUUCUUUAAGCU-5′ (SEQ ID NO: 346) MYC-731 Target:5′-CAGCGAGGATATCTGGAAGAAATTCGA-3′ (SEQ ID NO: 673)5′-CGUUGCGGUCACACCCUUCUCCCtt-3′ (SEQ ID NO: 20)3′-AUGCAACGCCAGUGUGGGAAGAGGGAA-5′ (SEQ ID NO: 347) MYC-816 Target:5′-TACGTTGCGGTCACACCCTTCTCCCTT-3′ (SEQ ID NO: 674)5′-ACAUGGUGAACCAGAGUUUCAUCtg-3′ (SEQ ID NO: 21)3′-UCUGUACCACUUGGUCUCAAAGUAGAC-5′ (SEQ ID NO: 348) MYC-920 Target:5′-AGACATGGTGAACCAGAGTTTCATCTG-3′ (SEQ ID NO: 675)5′-CCGGACGACGAGACCUUCAUCAAaa-3′ (SEQ ID NO: 22)3′-UGGGCCUGCUGCUCUGGAAGUAGUUUU-5′ (SEQ ID NO: 349) MYC-949 Target:5′-ACCCGGACGACGAGACCTTCATCAAAA-3′ (SEQ ID NO: 676)5′-GAGACCUUCAUCAAAAACAUCAUca-3′ (SEQ ID NO: 23)3′-UGCUCUGGAAGUAGUUUUUGUAGUAGU-5′ (SEQ ID NO: 350) MYC-958 Target:5′-ACGAGACCTTCATCAAAAACATCATCA-3′ (SEQ ID NO: 677)5′-AAAAACAUCAUCAUCCAGGACUGta-3′ (SEQ ID NO: 24)3′-AGUUUUUGUAGUAGUAGGUCCUGACAU-5′ (SEQ ID NO: 351) MYC-970 Target:5′-TCAAAAACATCATCATCCAGGACTGTA-3′ (SEQ ID NO: 678)5′-GGACUGUAUGUGGAGCGGCUUCUcg-3′ (SEQ ID NO: 25)3′-GUCCUGACAUACACCUCGCCGAAGAGC-5′ (SEQ ID NO: 352) MYC-987 Target:5′-CAGGACTGTATGTGGAGCGGCTTCTCG-3′ (SEQ ID NO: 679)5′-CUGCUCCACCUCCAGCUUGUACCtg-3′ (SEQ ID NO: 26)3′-CAGACGAGGUGGAGGUCGAACAUGGAC-5′ (SEQ ID NO: 353) MYC-1104 Target:5′-GTCTGCTCCACCTCCAGCTTGTACCTG-3′ (SEQ ID NO: 680)5′-ACCUCCAGCUUGUACCUGCAGGAtc-3′ (SEQ ID NO: 27)3′-GGUGGAGGUCGAACAUGGACGUCCUAG-5′ (SEQ ID NO: 354) MYC-1111 Target:5′-CCACCTCCAGCTTGTACCTGCAGGATC-3′ (SEQ ID NO: 681)5′-CAGCUUGUACCUGCAGGAUCUGAgc-3′ (SEQ ID NO: 28)3′-AGGUCGAACAUGGACGUCCUAGACUCG-5′ (SEQ ID NO: 355) MYC-1116 Target:5′-TCCAGCTTGTACCTGCAGGATCTGAGC-3′ (SEQ ID NO: 682)5′-AAGUCCUGCGCCUCGCAAGACUCca-3′ (SEQ ID NO: 29)3′-GGUUCAGGACGCGGAGCGUUCUGAGGU-5′ (SEQ ID NO: 356) MYC-1210 Target:5′-CCAAGTCCTGCGCCTCGCAAGACTCCA-3′ (SEQ ID NO: 683)5′-GCAGCGACUCUGAGGAGGAACAAga-3′ (SEQ ID NO: 30)3′-GUCGUCGCUGAGACUCCUCCUUGUUCU-5′ (SEQ ID NO: 357) MYC-1340 Target:5′-CAGCAGCGACTCTGAGGAGGAACAAGA-3′ (SEQ ID NO: 684)5′-ACUCUGAGGAGGAACAAGAAGAUga-3′ (SEQ ID NO: 31)3′-GCUGAGACUCCUCCUUGUUCUUCUACU-5′ (SEQ ID NO: 358) MYC-1346 Target:5′-CGACTCTGAGGAGGAACAAGAAGATGA-3′ (SEQ ID NO: 685)5′-GAGGAGGAACAAGAAGAUGAGGAag-3′ (SEQ ID NO: 32)3′-GACUCCUCCUUGUUCUUCUACUCCUUC-5′ (SEQ ID NO: 359) MYC-1351 Target:5′-CTGAGGAGGAACAAGAAGATGAGGAAG-3′ (SEQ ID NO: 686)5′-AACAAGAAGAUGAGGAAGAAAUCga-3′ (SEQ ID NO: 33)3′-CCUUGUUCUUCUACUCCUUCUUUAGCU-5′ (SEQ ID NO: 360) MYC-1358 Target:5′-GGAACAAGAAGATGAGGAAGAAATCGA-3′ (SEQ ID NO: 687)5′-AAGAUGAGGAAGAAAUCGAUGUUgt-3′ (SEQ ID NO: 34)3′-UCUUCUACUCCUUCUUUAGCUACAACA-5′ (SEQ ID NO: 361) MYC-1364 Target:5′-AGAAGATGAGGAAGAAATCGATGTTGT-3′ (SEQ ID NO: 688)5′-AGGAAGAAAUCGAUGUUGUUUCUgt-3′ (SEQ ID NO: 35)3′-ACUCCUUCUUUAGCUACAACAAAGACA-5′ (SEQ ID NO: 362) MYC-1370 Target:5′-TGAGGAAGAAATCGATGTTGTTTCTGT-3′ (SEQ ID NO: 689)5′-AAAUCGAUGUUGUUUCUGUGGAAaa-3′ (SEQ ID NO: 36)3′-UCUUUAGCUACAACAAAGACACCUUUU-5′ (SEQ ID NO: 363) MYC-1376 Target:5′-AGAAATCGATGTTGTTTCTGTGGAAAA-3′ (SEQ ID NO: 690)5′-AUGUUGUUUCUGUGGAAAAGAGGca-3′ (SEQ ID NO: 37)3′-GCUACAACAAAGACACCUUUUCUCCGU-5′ (SEQ ID NO: 364) MYC-1382 Target:5′-CGATGTTGTTTCTGTGGAAAAGAGGCA-3′ (SEQ ID NO: 691)5′-GAGGCAGGCUCCUGGCAAAAGGUca-3′ (SEQ ID NO: 38)3′-UUCUCCGUCCGAGGACCGUUUUCCAGU-5′ (SEQ ID NO: 365) MYC-1401 Target:5′-AAGAGGCAGGCTCCTGGCAAAAGGTCA-3′ (SEQ ID NO: 692)5′-AGGCUCCUGGCAAAAGGUCAGAGtc-3′ (SEQ ID NO: 39)3′-CGUCCGAGGACCGUUUUCCAGUCUCAG-5′ (SEQ ID NO: 366) MYC-1406 Target:5′-GCAGGCTCCTGGCAAAAGGTCAGAGTC-3′ (SEQ ID NO: 693)5′-CCUGGCAAAAGGUCAGAGUCUGGat-3′ (SEQ ID NO: 40)3′-GAGGACCGUUUUCCAGUCUCAGACCUA-5′ (SEQ ID NO: 367) MYC-1411 Target:5′-CTCCTGGCAAAAGGTCAGAGTCTGGAT-3′ (SEQ ID NO: 694)5′-CAAAAGGUCAGAGUCUGGAUCACct-3′ (SEQ ID NO: 41)3′-CCGUUUUCCAGUCUCAGACCUAGUGGA-5′ (SEQ ID NO: 368) MYC-1416 Target:5′-GGCAAAAGGTCAGAGTCTGGATCACCT-3′ (SEQ ID NO: 695)5′-GGUCAGAGUCUGGAUCACCUUCUgc-3′ (SEQ ID NO: 42)3′-UUCCAGUCUCAGACCUAGUGGAAGACG-5′ (SEQ ID NO: 369) MYC-1421 Target:5′-AAGGTCAGAGTCTGGATCACCTTCTGC-3′ (SEQ ID NO: 696)5′-GCAAACCUCCUCACAGCCCACUGgt-3′ (SEQ ID NO: 43)3′-GUCGUUUGGAGGAGUGUCGGGUGACCA-5′ (SEQ ID NO: 370) MYC-1457 Target:5′-CAGCAAACCTCCTCACAGCCCACTGGT-3′ (SEQ ID NO: 697)5′-CCUCACAGCCCACUGGUCCUCAAga-3′ (SEQ ID NO: 44)3′-GAGGAGUGUCGGGUGACCAGGAGUUCU-5′ (SEQ ID NO: 371) MYC-1465 Target:5′-CTCCTCACAGCCCACTGGTCCTCAAGA-3′ (SEQ ID NO: 698)5′-CCCUCCACUCGGAAGGACUAUCCtg-3′ (SEQ ID NO: 45)3′-GAGGGAGGUGAGCCUUCCUGAUAGGAC-5′ (SEQ ID NO: 372) MYC-1531 Target:5′-CTCCCTCCACTCGGAAGGACTATCCTG-3′ (SEQ ID NO: 699)5′-CUCGGAAGGACUAUCCUGCUGCCaa-3′ (SEQ ID NO: 46)3′-GUGAGCCUUCCUGAUAGGACGACGGUU-5′ (SEQ ID NO: 373) MYC-1538 Target:5′-CACTCGGAAGGACTATCCTGCTGCCAA-3′ (SEQ ID NO: 700)5′-AUCCUGCUGCCAAGAGGGUCAAGtt-3′ (SEQ ID NO: 47)3′-GAUAGGACGACGGUUCUCCCAGUUCAA-5′ (SEQ ID NO: 374) MYC-1550 Target:5′-CTATCCTGCTGCCAAGAGGGTCAAGTT-3′ (SEQ ID NO: 701)5′-GCUGCCAAGAGGGUCAAGUUGGAca-3′ (SEQ ID NO: 48)3′-GACGACGGUUCUCCCAGUUCAACCUGU-5′ (SEQ ID NO: 375) MYC-1555 Target:5′-CTGCTGCCAAGAGGGTCAAGTTGGACA-3′ (SEQ ID NO: 702)5′-CAAGAGGGUCAAGUUGGACAGUGtc-3′ (SEQ ID NO: 49)3′-CGGUUCUCCCAGUUCAACCUGUCACAG-5′ (SEQ ID NO: 376) MYC-1560 Target:5′-GCCAAGAGGGTCAAGTTGGACAGTGTC-3′ (SEQ ID NO: 703)5′-GGGUCAAGUUGGACAGUGUCAGAgt-3′ (SEQ ID NO: 50)3′-CUCCCAGUUCAACCUGUCACAGUCUCA-5′ (SEQ ID NO: 377) MYC-1565 Target:5′-GAGGGTCAAGTTGGACAGTGTCAGAGT-3′ (SEQ ID NO: 704)5′-AAGUUGGACAGUGUCAGAGUCCUga-3′ (SEQ ID NO: 51)3′-AGUUCAACCUGUCACAGUCUCAGGACU-5′ (SEQ ID NO: 378) MYC-1570 Target:5′-TCAAGTTGGACAGTGTCAGAGTCCTGA-3′ (SEQ ID NO: 705)5′-GGACAGUGUCAGAGUCCUGAGACag-3′ (SEQ ID NO: 52)3′-AACCUGUCACAGUCUCAGGACUCUGUC-5′ (SEQ ID NO: 379) MYC-1575 Target:5′-TTGGACAGTGTCAGAGTCCTGAGACAG-3′ (SEQ ID NO: 706)5′-CAGAGUCCUGAGACAGAUCAGCAac-3′ (SEQ ID NO: 53)3′-CAGUCUCAGGACUCUGUCUAGUCGUUG-5′ (SEQ ID NO: 380) MYC-1584 Target:5′-GTCAGAGTCCTGAGACAGATCAGCAAC-3′ (SEQ ID NO: 707)5′-GAGACAGAUCAGCAACAACCGAAaa-3′ (SEQ ID NO: 54)3′-GACUCUGUCUAGUCGUUGUUGGCUUUU-5′ (SEQ ID NO: 381) MYC-1593 Target:5′-CTGAGACAGATCAGCAACAACCGAAAA-3′ (SEQ ID NO: 708)5′-GAUCAGCAACAACCGAAAAUGCAcc-3′ (SEQ ID NO: 55)3′-GUCUAGUCGUUGUUGGCUUUUACGUGG-5′ (SEQ ID NO: 382) MYC-1599 Target:5′-CAGATCAGCAACAACCGAAAATGCACC-3′ (SEQ ID NO: 709)5′-CCUCGGACACCGAGGAGAAUGUCaa-3′ (SEQ ID NO: 56)3′-CAGGAGCCUGUGGCUCCUCUUACAGUU-5′ (SEQ ID NO: 383) MYC-1634 Target:5′-GTCCTCGGACACCGAGGAGAATGTCAA-3′ (SEQ ID NO: 710)5′-GACACCGAGGAGAAUGUCAAGAGgc-3′ (SEQ ID NO: 57)3′-GCCUGUGGCUCCUCUUACAGUUCUCCG-5′ (SEQ ID NO: 384) MYC-1639 Target:5′-CGGACACCGAGGAGAATGTCAAGAGGC-3′ (SEQ ID NO: 711)5′-CAGAGGAGGAACGAGCUAAAACGga-3′ (SEQ ID NO: 58)3′-CGGUCUCCUCCUUGCUCGAUUUUGCCU-5′ (SEQ ID NO: 385) MYC-1687 Target:5′-GCCAGAGGAGGAACGAGCTAAAACGGA-3′ (SEQ ID NO: 712)5′-AGGAACGAGCUAAAACGGAGCUUtt-3′ (SEQ ID NO: 59)3′-CCUCCUUGCUCGAUUUUGCCUCGAAAA-5′ (SEQ ID NO: 386) MYC-1693 Target:5′-GGAGGAACGAGCTAAAACGGAGCTTTT-3′ (SEQ ID NO: 713)5′-CGAGCUAAAACGGAGCUUUUUUGcc-3′ (SEQ ID NO: 60)3′-UUGCUCGAUUUUGCCUCGAAAAAACGG-5′ (SEQ ID NO: 387) MYC-1698 Target:5′-AACGAGCTAAAACGGAGCTTTTTTGCC-3′ (SEQ ID NO: 714)5′-AAAACGGAGCUUUUUUGCCCUGCgt-3′ (SEQ ID NO: 61)3′-GAUUUUGCCUCGAAAAAACGGGACGCA-5′ (SEQ ID NO: 388) MYC-1704 Target:5′-CTAAAACGGAGCTTTTTTGCCCTGCGT-3′ (SEQ ID NO: 715)5′-GGAGCUUUUUUGCCCUGCGUGACca-3′ (SEQ ID NO: 62)3′-UGCCUCGAAAAAACGGGACGCACUGGU-5′ (SEQ ID NO: 389) MYC-1709 Target:5′-ACGGAGCTTTTTTGCCCTGCGTGACCA-3′ (SEQ ID NO: 716)5′-GACCAGAUCCCGGAGUUGGAAAAca-3′ (SEQ ID NO: 63)3′-CACUGGUCUAGGGCCUCAACCUUUUGU-5′ (SEQ ID NO: 390) MYC-1729 Target:5′-GTGACCAGATCCCGGAGTTGGAAAACA-3′ (SEQ ID NO: 717)5′-GAUCCCGGAGUUGGAAAACAAUGaa-3′ (SEQ ID NO: 64)3′-GUCUAGGGCCUCAACCUUUUGUUACUU-5′ (SEQ ID NO: 391) MYC-1734 Target:5′-CAGATCCCGGAGTTGGAAAACAATGAA-3′ (SEQ ID NO: 718)5′-CGGAGUUGGAAAACAAUGAAAAGgc-3′ (SEQ ID NO: 65)3′-GGGCCUCAACCUUUUGUUACUUUUCCG-5′ (SEQ ID NO: 392) MYC-1739 Target:5′-CCCGGAGTTGGAAAACAATGAAAAGGC-3′ (SEQ ID NO: 719)5′-AGGUAGUUAUCCUUAAAAAAGCCac-3′ (SEQ ID NO: 66)3′-GUUCCAUCAAUAGGAAUUUUUUCGGUG-5′ (SEQ ID NO: 393) MYC-1769 Target:5′-CAAGGTAGTTATCCTTAAAAAAGCCAC-3′ (SEQ ID NO: 720)5′-GUUAUCCUUAAAAAAGCCACAGCat-3′ (SEQ ID NO: 67)3′-AUCAAUAGGAAUUUUUUCGGUGUCGUA-5′ (SEQ ID NO: 394) MYC-1774 Target:5′-TAGTTATCCTTAAAAAAGCCACAGCAT-3′ (SEQ ID NO: 721)5′-CCUUAAAAAAGCCACAGCAUACAtc-3′ (SEQ ID NO: 68)3′-UAGGAAUUUUUUCGGUGUCGUAUGUAG-5′ (SEQ ID NO: 395) MYC-1779 Target:5′-ATCCTTAAAAAAGCCACAGCATACATC-3′ (SEQ ID NO: 722)5′-AAAAAGCCACAGCAUACAUCCUGtc-3′ (SEQ ID NO: 69)3′-AUUUUUUCGGUGUCGUAUGUAGGACAG-5′ (SEQ ID NO: 396) MYC-1784 Target:5′-TAAAAAAGCCACAGCATACATCCTGTC-3′ (SEQ ID NO: 723)5′-GCCACAGCAUACAUCCUGUCCGUcc-3′ (SEQ ID NO: 70)3′-UUCGGUGUCGUAUGUAGGACAGGCAGG-5′ (SEQ ID NO: 397) MYC-1789 Target:5′-AAGCCACAGCATACATCCTGTCCGTCC-3′ (SEQ ID NO: 724)5′-GCAUACAUCCUGUCCGUCCAAGCag-3′ (SEQ ID NO: 71)3′-GUCGUAUGUAGGACAGGCAGGUUCGUC-5′ (SEQ ID NO: 398) MYC-1795 Target:5′-CAGCATACATCCTGTCCGTCCAAGCAG-3′ (SEQ ID NO: 725)5′-CCUGUCCGUCCAAGCAGAGGAGCaa-3′ (SEQ ID NO: 72)3′-UAGGACAGGCAGGUUCGUCUCCUCGUU-5′ (SEQ ID NO: 399) MYC-1803 Target:5′-ATCCTGTCCGTCCAAGCAGAGGAGCAA-3′ (SEQ ID NO: 726)5′-CCGUCCAAGCAGAGGAGCAAAAGct-3′ (SEQ ID NO: 73)3′-CAGGCAGGUUCGUCUCCUCGUUUUCGA-5′ (SEQ ID NO: 400) MYC-1808 Target:5′-GTCCGTCCAAGCAGAGGAGCAAAAGCT-3′ (SEQ ID NO: 727)5′-GCAGAGGAGCAAAAGCUCAUUUCtg-3′ (SEQ ID NO: 74)3′-UUCGUCUCCUCGUUUUCGAGUAAAGAC-5′ (SEQ ID NO: 401) MYC-1816 Target:5′-AAGCAGAGGAGCAAAAGCTCATTTCTG-3′ (SEQ ID NO: 728)5′-AGCAAAAGCUCAUUUCUGAAGAGga-3′ (SEQ ID NO: 75)3′-CCUCGUUUUCGAGUAAAGACUUCUCCU-5′ (SEQ ID NO: 402) MYC-1823 Target:5′-GGAGCAAAAGCTCATTTCTGAAGAGGA-3′ (SEQ ID NO: 729)5′-AAGCUCAUUUCUGAAGAGGACUUgt-3′ (SEQ ID NO: 76)3′-UUUUCGAGUAAAGACUUCUCCUGAACA-5′ (SEQ ID NO: 403) MYC-1828 Target:5′-AAAAGCTCATTTCTGAAGAGGACTTGT-3′ (SEQ ID NO: 730)5′-AUUUCUGAAGAGGACUUGUUGCGga-3′ (SEQ ID NO: 77)3′-AGUAAAGACUUCUCCUGAACAACGCCU-5′ (SEQ ID NO: 404) MYC-1834 Target:5′-TCATTTCTGAAGAGGACTTGTTGCGGA-3′ (SEQ ID NO: 731)5′-GAAGAGGACUUGUUGCGGAAACGac-3′ (SEQ ID NO: 78)3′-GACUUCUCCUGAACAACGCCUUUGCUG-5′ (SEQ ID NO: 405) MYC-1840 Target:5′-CTGAAGAGGACTTGTTGCGGAAACGAC-3′ (SEQ ID NO: 732)5′-GGACUUGUUGCGGAAACGACGAGaa-3′ (SEQ ID NO: 79)3′-CUCCUGAACAACGCCUUUGCUGCUCUU-5′ (SEQ ID NO: 406) MYC-1845 Target:5′-GAGGACTTGTTGCGGAAACGACGAGAA-3′ (SEQ ID NO: 733)5′-UGUUGCGGAAACGACGAGAACAGtt-3′ (SEQ ID NO: 80)3′-GAACAACGCCUUUGCUGCUCUUGUCAA-5′ (SEQ ID NO: 407) MYC-1850 Target:5′-CTTGTTGCGGAAACGACGAGAACAGTT-3′ (SEQ ID NO: 734)5′-CGGAAACGACGAGAACAGUUGAAac-3′ (SEQ ID NO: 81)3′-ACGCCUUUGCUGCUCUUGUCAACUUUG-5′ (SEQ ID NO: 408) MYC-1855 Target:5′-TGCGGAAACGACGAGAACAGTTGAAAC-3′ (SEQ ID NO: 735)5′-AAACUUGAACAGCUACGGAACUCtt-3′ (SEQ ID NO: 82)3′-UGUUUGAACUUGUCGAUGCCUUGAGAA-5′ (SEQ ID NO: 409) MYC-1882 Target:5′-ACAAACTTGAACAGCTACGGAACTCTT-3′ (SEQ ID NO: 736)5′-GAACAGCUACGGAACUCUUGUGCgt-3′ (SEQ ID NO: 83)3′-AACUUGUCGAUGCCUUGAGAACACGCA-5′ (SEQ ID NO: 410) MYC-1888 Target:5′-TTGAACAGCTACGGAACTCTTGTGCGT-3′ (SEQ ID NO: 737)5′-GCUACGGAACUCUUGUGCGUAAGga-3′ (SEQ ID NO: 84)3′-GUCGAUGCCUUGAGAACACGCAUUCCU-5′ (SEQ ID NO: 411) MYC-1893 Target:5′-CAGCTACGGAACTCTTGTGCGTAAGGA-3′ (SEQ ID NO: 738)5′-AACUCUUGUGCGUAAGGAAAAGUaa-3′ (SEQ ID NO: 85)3′-CCUUGAGAACACGCAUUCCUUUUCAUU-5′ (SEQ ID NO: 412) MYC-1900 Target:5′-GGAACTCTTGTGCGTAAGGAAAAGTAA-3′ (SEQ ID NO: 739)5′-UGUGCGUAAGGAAAAGUAAGGAAaa-3′ (SEQ ID NO: 86)3′-GAACACGCAUUCCUUUUCAUUCCUUUU-5′ (SEQ ID NO: 413) MYC-1906 Target:5′-CTTGTGCGTAAGGAAAAGTAAGGAAAA-3′ (SEQ ID NO: 740)5′-GUAAGGAAAAGUAAGGAAAACGAtt-3′ (SEQ ID NO: 87)3′-CGCAUUCCUUUUCAUUCCUUUUGCUAA-5′ (SEQ ID NO: 414) MYC-1911 Target:5′-GCGTAAGGAAAAGTAAGGAAAACGATT-3′ (SEQ ID NO: 741)5′-GUAAGGAAAACGAUUCCUUCUAAca-3′ (SEQ ID NO: 88)3′-UUCAUUCCUUUUGCUAAGGAAGAUUGU-5′ (SEQ ID NO: 415) MYC-1921 Target:5′-AAGTAAGGAAAACGATTCCTTCTAACA-3′ (SEQ ID NO: 742)5′-GAAAACGAUUCCUUCUAACAGAAat-3′ (SEQ ID NO: 89)3′-UCCUUUUGCUAAGGAAGAUUGUCUUUA-5′ (SEQ ID NO: 416) MYC-1926 Target:5′-AGGAAAACGATTCCTTCTAACAGAAAT-3′ (SEQ ID NO: 743)5′-CGAUUCCUUCUAACAGAAAUGUCct-3′ (SEQ ID NO: 90)3′-UUGCUAAGGAAGAUUGUCUUUACAGGA-5′ (SEQ ID NO: 417) MYC-1931 Target:5′-AACGATTCCTTCTAACAGAAATGTCCT-3′ (SEQ ID NO: 744)5′-CUUCUAACAGAAAUGUCCUGAGCaa-3′ (SEQ ID NO: 91)3′-AGGAAGAUUGUCUUUACAGGACUCGUU-5′ (SEQ ID NO: 418) MYC-1937 Target:5′-TCCTTCTAACAGAAATGTCCTGAGCAA-3′ (SEQ ID NO: 745)5′-CAGAAAUGUCCUGAGCAAUCACCta-3′ (SEQ ID NO: 92)3′-UUGUCUUUACAGGACUCGUUAGUGGAU-5′ (SEQ ID NO: 419) MYC-1944 Target:5′-AACAGAAATGTCCTGAGCAATCACCTA-3′ (SEQ ID NO: 746)5′-CCUGAGCAAUCACCUAUGAACUUgt-3′ (SEQ ID NO: 93)3′-CAGGACUCGUUAGUGGAUACUUGAACA-5′ (SEQ ID NO: 420) MYC-1953 Target:5′-GTCCTGAGCAATCACCTATGAACTTGT-3′ (SEQ ID NO: 747)5′-CAAUCACCUAUGAACUUGUUUCAaa-3′ (SEQ ID NO: 94)3′-UCGUUAGUGGAUACUUGAACAAAGUUU-5′ (SEQ ID NO: 421) MYC-1959 Target:5′-AGCAATCACCTATGAACTTGTTTCAAA-3′ (SEQ ID NO: 748)5′-CCUAUGAACUUGUUUCAAAUGCAtg-3′ (SEQ ID NO: 95)3′-GUGGAUACUUGAACAAAGUUUACGUAC-5′ (SEQ ID NO: 422) MYC-1965 Target:5′-CACCTATGAACTTGTTTCAAATGCATG-3′ (SEQ ID NO: 749)5′-GAACUUGUUUCAAAUGCAUGAUCaa-3′ (SEQ ID NO: 96)3′-UACUUGAACAAAGUUUACGUACUAGUU-5′ (SEQ ID NO: 423) MYC-1970 Target:5′-ATGAACTTGTTTCAAATGCATGATCAA-3′ (SEQ ID NO: 750)5′-GUUUCAAAUGCAUGAUCAAAUGCaa-3′ (SEQ ID NO: 97)3′-AACAAAGUUUACGUACUAGUUUACGUU-5′ (SEQ ID NO: 424) MYC-1976 Target:5′-TTGTTTCAAATGCATGATCAAATGCAA-3′ (SEQ ID NO: 751)5′-AAAUGCAUGAUCAAAUGCAACCUca-3′ (SEQ ID NO: 98)3′-AGUUUACGUACUAGUUUACGUUGGAGU-5′ (SEQ ID NO: 425) MYC-1981 Target:5′-TCAAATGCATGATCAAATGCAACCTCA-3′ (SEQ ID NO: 752)5′-GAUCAAAUGCAACCUCACAACCUtg-3′ (SEQ ID NO: 99)3′-UACUAGUUUACGUUGGAGUGUUGGAAC-5′ (SEQ ID NO: 426) MYC-1989 Target:5′-ATGATCAAATGCAACCTCACAACCTTG-3′ (SEQ ID NO: 753)5′-AAUGCAACCUCACAACCUUGGCUga-3′ (SEQ ID NO: 100)3′-GUUUACGUUGGAGUGUUGGAACCGACU-5′ (SEQ ID NO: 427) MYC-1994 Target:5′-CAAATGCAACCTCACAACCTTGGCTGA-3′ (SEQ ID NO: 754)5′-CCUCACAACCUUGGCUGAGUCUUga-3′ (SEQ ID NO: 101)3′-UUGGAGUGUUGGAACCGACUCAGAACU-5′ (SEQ ID NO: 428) MYC-2001 Target:5′-AACCTCACAACCTTGGCTGAGTCTTGA-3′ (SEQ ID NO: 755)5′-CAACCUUGGCUGAGUCUUGAGACtg-3′ (SEQ ID NO: 102)3′-GUGUUGGAACCGACUCAGAACUCUGAC-5′ (SEQ ID NO: 429) MYC-2006 Target:5′-CACAACCTTGGCTGAGTCTTGAGACTG-3′ (SEQ ID NO: 756)5′-GGCUGAGUCUUGAGACUGAAAGAtt-3′ (SEQ ID NO: 103)3′-AACCGACUCAGAACUCUGACUUUCUAA-5′ (SEQ ID NO: 430) MYC-2013 Target:5′-TTGGCTGAGTCTTGAGACTGAAAGATT-3′ (SEQ ID NO: 757)5′-GUCUUGAGACUGAAAGAUUUAGCca-3′ (SEQ ID NO: 104)3′-CUCAGAACUCUGACUUUCUAAAUCGGU-5′ (SEQ ID NO: 431) MYC-2019 Target:5′-GAGTCTTGAGACTGAAAGATTTAGCCA-3′ (SEQ ID NO: 758)5′-GACUGAAAGAUUUAGCCAUAAUGta-3′ (SEQ ID NO: 105)3′-CUCUGACUUUCUAAAUCGGUAUUACAU-5′ (SEQ ID NO: 432) MYC-2026 Target:5′-GAGACTGAAAGATTTAGCCATAATGTA-3′ (SEQ ID NO: 759)5′-AAAGAUUUAGCCAUAAUGUAAACtg-3′ (SEQ ID NO: 106)3′-ACUUUCUAAAUCGGUAUUACAUUUGAC-5′ (SEQ ID NO: 433) MYC-2031 Target:5′-TGAAAGATTTAGCCATAATGTAAACTG-3′ (SEQ ID NO: 760)5′-GCCAUAAUGUAAACUGCCUCAAAtt-3′ (SEQ ID NO: 107)3′-AUCGGUAUUACAUUUGACGGAGUUUAA-5′ (SEQ ID NO: 434) MYC-2040 Target:5′-TAGCCATAATGTAAACTGCCTCAAATT-3′ (SEQ ID NO: 761)5′-GUAAACUGCCUCAAAUUGGACUUtg-3′ (SEQ ID NO: 108)3′-UACAUUUGACGGAGUUUAACCUGAAAC-5′ (SEQ ID NO: 435) MYC-2048 Target:5′-ATGTAAACTGCCTCAAATTGGACTTTG-3′ (SEQ ID NO: 762)5′-UGCCUCAAAUUGGACUUUGGGCAta-3′ (SEQ ID NO: 109)3′-UGACGGAGUUUAACCUGAAACCCGUAU-5′ (SEQ ID NO: 436) MYC-2054 Target:5′-ACTGCCTCAAATTGGACTTTGGGCATA-3′ (SEQ ID NO: 763)5′-CAAAUUGGACUUUGGGCAUAAAAga-3′ (SEQ ID NO: 110)3′-GAGUUUAACCUGAAACCCGUAUUUUCU-5′ (SEQ ID NO: 437) MYC-2059 Target:5′-CTCAAATTGGACTTTGGGCATAAAAGA-3′ (SEQ ID NO: 764)5′-GACUUUGGGCAUAAAAGAACUUUtt-3′ (SEQ ID NO: 111)3′-ACCUGAAACCCGUAUUUUCUUGAAAAA-5′ (SEQ ID NO: 438) MYC-2066 Target:5′-TGGACTTTGGGCATAAAAGAACTTTTT-3′ (SEQ ID NO: 765)5′-GGCAUAAAAGAACUUUUUUAUGCtt-3′ (SEQ ID NO: 112)3′-ACCCGUAUUUUCUUGAAAAAAUACGAA-5′ (SEQ ID NO: 439) MYC-2073 Target:5′-TGGGCATAAAAGAACTTTTTTATGCTT-3′ (SEQ ID NO: 766)5′-AAAAGAACUUUUUUAUGCUUACCat-3′ (SEQ ID NO: 113)3′-UAUUUUCUUGAAAAAAUACGAAUGGUA-5′ (SEQ ID NO: 440) MYC-2078 Target:5′-ATAAAAGAACTTTTTTATGCTTACCAT-3′ (SEQ ID NO: 767)5′-AACUUUUUUAUGCUUACCAUCUUtt-3′ (SEQ ID NO: 114)3′-UCUUGAAAAAAUACGAAUGGUAGAAAA-5′ (SEQ ID NO: 441) MYC-2083 Target:5′-AGAACTTTTTTATGCTTACCATCTTTT-3′ (SEQ ID NO: 768)5′-UUUAUGCUUACCAUCUUUUUUUUtt-3′ (SEQ ID NO: 115)3′-AAAAAUACGAAUGGUAGAAAAAAAAAA-5′ (SEQ ID NO: 442) MYC-2089 Target:5′-TTTTTATGCTTACCATCTTTTTTTTTT-3′ (SEQ ID NO: 769)5′-GCUUACCAUCUUUUUUUUUUCUUta-3′ (SEQ ID NO: 116)3′-UACGAAUGGUAGAAAAAAAAAAGAAAU-5′ (SEQ ID NO: 443) MYC-2094 Target:5′-ATGCTTACCATCTTTTTTTTTTCTTTA-3′ (SEQ ID NO: 770)5′-CCAUCUUUUUUUUUUCUUUAACAga-3′ (SEQ ID NO: 117)3′-AUGGUAGAAAAAAAAAAGAAAUUGUCU-5′ (SEQ ID NO: 444) MYC-2099 Target:5′-TACCATCTTTTTTTTTTCTTTAACAGA-3′ (SEQ ID NO: 771)5′-UUUUUUUUUCUUUAACAGAUUUGta-3′ (SEQ ID NO: 118)3′-GAAAAAAAAAAGAAAUUGUCUAAACAU-5′ (SEQ ID NO: 445) MYC-2105 Target:5′-CTTTTTTTTTTCTTTAACAGATTTGTA-3′ (SEQ ID NO: 772)5′-CUUUAACAGAUUUGUAUUUAAGAat-3′ (SEQ ID NO: 119)3′-AAGAAAUUGUCUAAACAUAAAUUCUUA-5′ (SEQ ID NO: 446) MYC-2114 Target:5′-TTCTTTAACAGATTTGTATTTAAGAAT-3′ (SEQ ID NO: 773)5′-CAGAUUUGUAUUUAAGAAUUGUUtt-3′ (SEQ ID NO: 120)3′-UUGUCUAAACAUAAAUUCUUAACAAAA-5′ (SEQ ID NO: 447) MYC-2120 Target:5′-AACAGATTTGTATTTAAGAATTGTTTT-3′ (SEQ ID NO: 774)5′-UAUUUAAGAAUUGUUUUUAAAAAat-3′ (SEQ ID NO: 121)3′-ACAUAAAUUCUUAACAAAAAUUUUUUA-5′ (SEQ ID NO: 448) MYC-2128 Target:5′-TGTATTTAAGAATTGTTTTTAAAAAAT-3′ (SEQ ID NO: 775)5′-GAAUUGUUUUUAAAAAAUUUUAAga-3′ (SEQ ID NO: 122)3′-UUCUUAACAAAAAUUUUUUAAAAUUCU-5′ (SEQ ID NO: 449) MYC-2135 Target:5′-AAGAATTGTTTTTAAAAAATTTTAAGA-3′ (SEQ ID NO: 776)5′-AAUGUUUCUCUGUAAAUAUUGCCat-3′ (SEQ ID NO: 123)3′-UGUUACAAAGAGACAUUUAUAACGGUA-5′ (SEQ ID NO: 450) MYC-2167 Target:5′-ACAATGTTTCTCTGTAAATATTGCCAT-3′ (SEQ ID NO: 777)5′-CUGUAAAUAUUGCCAUUAAAUGUaa-3′ (SEQ ID NO: 124)3′-GAGACAUUUAUAACGGUAAUUUACAUU-5′ (SEQ ID NO: 451) MYC-2176 Target:5′-CTCTGTAAATATTGCCATTAAATGTAA-3′ (SEQ ID NO: 778)5′-AAUAUUGCCAUUAAAUGUAAAUAac-3′ (SEQ ID NO: 125)3′-AUUUAUAACGGUAAUUUACAUUUAUUG-5′ (SEQ ID NO: 452) MYC-2181 Target:5′-TAAATATTGCCATTAAATGTAAATAAC-3′ (SEQ ID NO: 779)5′-CCAUUAAAUGUAAAUAACUUUAAta-3′ (SEQ ID NO: 126)3′-ACGGUAAUUUACAUUUAUUGAAAUUAU-5′ (SEQ ID NO: 453) MYC-2188 Target:5′-TGCCATTAAATGTAAATAACTTTAATA-3′ (SEQ ID NO: 780)5′-UUAAUAAAACGUUUAUAGCAGUUac-3′ (SEQ ID NO: 127)3′-GAAAUUAUUUUGCAAAUAUCGUCAAUG-5′ (SEQ ID NO: 454) MYC-2207 Target:5′-CTTTAATAAAACGTTTATAGCAGTTAC-3′ (SEQ ID NO: 781)5′-CAGAAUUUCAAUCCUAGUAUAUAgt-3′ (SEQ ID NO: 128)3′-GUGUCUUAAAGUUAGGAUCAUAUAUCA-5′ (SEQ ID NO: 455) MYC-2233 Target:5′-CACAGAATTTCAATCCTAGTATATAGT-3′ (SEQ ID NO: 782)5′-CUAGUAUUAUAGGUACUAUAAACcc-3′ (SEQ ID NO: 129)3′-UGGAUCAUAAUAUCCAUGAUAUUUGGG-5′ (SEQ ID NO: 456) MYC-2260 Target:5′-ACCTAGTATTATAGGTACTATAAACCC-3′ (SEQ ID NO: 783)5′-UAUAGGUACUAUAAACCCUAAUUtt-3′ (SEQ ID NO: 130)3′-UAAUAUCCAUGAUAUUUGGGAUUAAAA-5′ (SEQ ID NO: 457) MYC-2267 Target:5′-ATTATAGGTACTATAAACCCTAATTTT-3′ (SEQ ID NO: 784)5′-ACUAUAAACCCUAAUUUUUUUUAtt-3′ (SEQ ID NO: 131)3′-CAUGAUAUUUGGGAUUAAAAAAAAUAA-5′ (SEQ ID NO: 458) MYC-2274 Target:5′-GTACTATAAACCCTAATTTTTTTTATT-3′ (SEQ ID NO: 785)5′-CCCUAAUUUUUUUUAUUUAAGUAca-3′ (SEQ ID NO: 132)3′-UUGGGAUUAAAAAAAAUAAAUUCAUGU-5′ (SEQ ID NO: 459) MYC-2282 Target:5′-AACCCTAATTTTTTTTATTTAAGTACA-3′ (SEQ ID NO: 786)5′-AUUUUUUUUAUUUAAGUACAUUUtg-3′ (SEQ ID NO: 133)3′-AUUAAAAAAAAUAAAUUCAUGUAAAAC-5′ (SEQ ID NO: 460) MYC-2287 Target:5′-TAATTTTTTTTATTTAAGTACATTTTG-3′ (SEQ ID NO: 787)5′-UAUUUAAGUACAUUUUGCUUUUUaa-3′ (SEQ ID NO: 134)3′-AAAUAAAUUCAUGUAAAACGAAAAAUU-5′ (SEQ ID NO: 461) MYC-2295 Target:5′-TTTATTTAAGTACATTTTGCTTTTTAA-3′ (SEQ ID NO: 788)5′-AAGUACAUUUUGCUUUUUAAAGUtg-3′ (SEQ ID NO: 135)3′-AAUUCAUGUAAAACGAAAAAUUUCAAC-5′ (SEQ ID NO: 462) MYC-2300 Target:5′-TTAAGTACATTTTGCTTTTTAAAGTTG-3′ (SEQ ID NO: 789)5′-AUUUUGCUUUUUAAAGUUGAUUUtt-3′ (SEQ ID NO: 136)3′-UGUAAAACGAAAAAUUUCAACUAAAAA-5′ (SEQ ID NO: 463) MYC-2306 Target:5′-ACATTTTGCTTTTTAAAGTTGATTTTT-3′ (SEQ ID NO: 790)5′-CUUUUUAAAGUUGAUUUUUUUCUat-3′ (SEQ ID NO: 137)3′-ACGAAAAAUUUCAACUAAAAAAAGAUA-5′ (SEQ ID NO: 464) MYC-2312 Target:5′-TGCTTTTTAAAGTTGATTTTTTTCTAT-3′ (SEQ ID NO: 791)5′-UAUUGUUUUUAGAAAAAAUAAAAta-3′ (SEQ ID NO: 138)3′-AGAUAACAAAAAUCUUUUUUAUUUUAU-5′ (SEQ ID NO: 465) MYC-2334 Target:5′-TCTATTGTTTTTAGAAAAAATAAAATA-3′ (SEQ ID NO: 792)5′-UUUUUAGAAAAAAUAAAAUAACUgg-3′ (SEQ ID NO: 139)3′-ACAAAAAUCUUUUUUAUUUUAUUGACC-5′ (SEQ ID NO: 466) MYC-2339 Target:5′-TGTTTTTAGAAAAAATAAAATAACTGG-3′ (SEQ ID NO: 793)5′-AAAAAUAAAAUAACUGGCAAAUAta-3′ (SEQ ID NO: 140)3′-CUUUUUUAUUUUAUUGACCGUUUAUAU-5′ (SEQ ID NO: 467) MYC-2347 Target:5′-GAAAAAATAAAATAACTGGCAAATATA-3′ (SEQ ID NO: 794)5′-AAUAACUGGCAAAUAUAUCAUUGag-3′ (SEQ ID NO: 141)3′-UUUUAUUGACCGUUUAUAUAGUAACUC-5′ (SEQ ID NO: 468) MYC-2355 Target:5′-AAAATAACTGGCAAATATATCATTGAG-3′ (SEQ ID NO: 795)5′-CAAAUAUAUCAUUGAGCCAAAUCtt-3′ (SEQ ID NO: 142)3′-CCGUUUAUAUAGUAACUCGGUUUAGAA-5′ (SEQ ID NO: 469) MYC-2364 Target:5′-GGCAAATATATCATTGAGCCAAATCTT-3′ (SEQ ID NO: 796)5′-AUCAUUGAGCCAAAUCUUAAAAAaa-3′ (SEQ ID NO: 143)3′-UAUAGUAACUCGGUUUAGAAUUUUUUU-5′ (SEQ ID NO: 470) MYC-2371 Target:5′-ATATCATTGAGCCAAATCTTAAAAAAA-3′ (SEQ ID NO: 797)5′-GAGCCAAAUCUUAAAAAAAAAAAaa-3′ (SEQ ID NO: 144)3′-AACUCGGUUUAGAAUUUUUUUUUUUUU-5′ (SEQ ID NO: 471) MYC-2377 Target:5′-TTGAGCCAAATCTTAAAAAAAAAAAAA-3′ (SEQ ID NO: 798)5′-ACUCGCUGUAGUAAUUCCAGCGAga-3′ (SEQ ID NO: 145)3′-AUUGAGCGACAUCAUUAAGGUCGCUCU-5′ (SEQ ID NO: 472) MYC-188 Target:5′-TAACTCGCTGTAGTAATTCCAGCGAGA-3′ (SEQ ID NO: 799)5′-CUCGCUGUAGUAAUUCCAGCGAGag-3′ (SEQ ID NO: 146)3′-UUGAGCGACAUCAUUAAGGUCGCUCUC-5′ (SEQ ID NO: 473) MYC-189 Target:5′-AACTCGCTGTAGTAATTCCAGCGAGAG-3′ (SEQ ID NO: 800)5′-UCGCUGUAGUAAUUCCAGCGAGAgg-3′ (SEQ ID NO: 147)3′-UGAGCGACAUCAUUAAGGUCGCUCUCC-5′ (SEQ ID NO: 474) MYC-190 Target:5′-ACTCGCTGTAGTAATTCCAGCGAGAGG-3′ (SEQ ID NO: 801)5′-CGCUGUAGUAAUUCCAGCGAGAGgc-3′ (SEQ ID NO: 148)3′-GAGCGACAUCAUUAAGGUCGCUCUCCG-5′ (SEQ ID NO: 475) MYC-191 Target:5′-CTCGCTGTAGTAATTCCAGCGAGAGGC-3′ (SEQ ID NO: 802)5′-GCUGUAGUAAUUCCAGCGAGAGGca-3′ (SEQ ID NO: 149)3′-AGCGACAUCAUUAAGGUCGCUCUCCGU-5′ (SEQ ID NO: 476) MYC-192 Target:5′-TCGCTGTAGTAATTCCAGCGAGAGGCA-3′ (SEQ ID NO: 803)5′-CUGUAGUAAUUCCAGCGAGAGGCag-3′ (SEQ ID NO: 150)3′-GCGACAUCAUUAAGGUCGCUCUCCGUC-5′ (SEQ ID NO: 477) MYC-193 Target:5′-CGCTGTAGTAATTCCAGCGAGAGGCAG-3′ (SEQ ID NO: 804)5′-UGUAGUAAUUCCAGCGAGAGGCAga-3′ (SEQ ID NO: 151)3′-CGACAUCAUUAAGGUCGCUCUCCGUCU-5′ (SEQ ID NO: 478) MYC-194 Target:5′-GCTGTAGTAATTCCAGCGAGAGGCAGA-3′ (SEQ ID NO: 805)5′-GUAGUAAUUCCAGCGAGAGGCAGag-3′ (SEQ ID NO: 152)3′-GACAUCAUUAAGGUCGCUCUCCGUCUC-5′ (SEQ ID NO: 479) MYC-195 Target:5′-CTGTAGTAATTCCAGCGAGAGGCAGAG-3′ (SEQ ID NO: 806)5′-CUUCACCAACAGGAACUAUGACCtc-3′ (SEQ ID NO: 153)3′-UCGAAGUGGUUGUCCUUGAUACUGGAG-5′ (SEQ ID NO: 480) MYC-612 Target:5′-AGCTTCACCAACAGGAACTATGACCTC-3′ (SEQ ID NO: 807)5′-UUCACCAACAGGAACUAUGACCUcg-3′ (SEQ ID NO: 154)3′-CGAAGUGGUUGUCCUUGAUACUGGAGC-5′ (SEQ ID NO: 481) MYC-613 Target:5′-GCTTCACCAACAGGAACTATGACCTCG-3′ (SEQ ID NO: 808)5′-UCACCAACAGGAACUAUGACCUCga-3′ (SEQ ID NO: 155)3′-GAAGUGGUUGUCCUUGAUACUGGAGCU-5′ (SEQ ID NO: 482) MYC-614 Target:5′-CTTCACCAACAGGAACTATGACCTCGA-3′ (SEQ ID NO: 809)5′-CACCAACAGGAACUAUGACCUCGac-3′ (SEQ ID NO: 156)3′-AAGUGGUUGUCCUUGAUACUGGAGCUG-5′ (SEQ ID NO: 483) MYC-615 Target:5′-TTCACCAACAGGAACTATGACCTCGAC-3′ (SEQ ID NO: 810)5′-ACCAACAGGAACUAUGACCUCGAct-3′ (SEQ ID NO: 157)3′-AGUGGUUGUCCUUGAUACUGGAGCUGA-5′ (SEQ ID NO: 484) MYC-616 Target:5′-TCACCAACAGGAACTATGACCTCGACT-3′ (SEQ ID NO: 811)5′-CCAACAGGAACUAUGACCUCGACta-3′ (SEQ ID NO: 158)3′-GUGGUUGUCCUUGAUACUGGAGCUGAU-5′ (SEQ ID NO: 485) MYC-617 Target:5′-CACCAACAGGAACTATGACCTCGACTA-3′ (SEQ ID NO: 812)5′-CAACAGGAACUAUGACCUCGACUac-3′ (SEQ ID NO: 159)3′-UGGUUGUCCUUGAUACUGGAGCUGAUG-5′ (SEQ ID NO: 486) MYC-618 Target:5′-ACCAACAGGAACTATGACCTCGACTAC-3′ (SEQ ID NO: 813)5′-AACAGGAACUAUGACCUCGACUAcg-3′ (SEQ ID NO: 160)3′-GGUUGUCCUUGAUACUGGAGCUGAUGC-5′ (SEQ ID NO: 487) MYC-619 Target:5′-CCAACAGGAACTATGACCTCGACTACG-3′ (SEQ ID NO: 814)5′-ACAGGAACUAUGACCUCGACUACga-3′ (SEQ ID NO: 161)3′-GUUGUCCUUGAUACUGGAGCUGAUGCU-5′ (SEQ ID NO: 488) MYC-620 Target:5′-CAACAGGAACTATGACCTCGACTACGA-3′ (SEQ ID NO: 815)5′-CAGGAACUAUGACCUCGACUACGac-3′ (SEQ ID NO: 162)3′-UUGUCCUUGAUACUGGAGCUGAUGCUG-5′ (SEQ ID NO: 489) MYC-621 Target:5′-AACAGGAACTATGACCTCGACTACGAC-3′ (SEQ ID NO: 816)5′-AGGAACUAUGACCUCGACUACGAct-3′ (SEQ ID NO: 163)3′-UGUCCUUGAUACUGGAGCUGAUGCUGA-5′ (SEQ ID NO: 490) MYC-622 Target:5′-ACAGGAACTATGACCTCGACTACGACT-3′ (SEQ ID NO: 817)5′-GGAACUAUGACCUCGACUACGACtc-3′ (SEQ ID NO: 164)3′-GUCCUUGAUACUGGAGCUGAUGCUGAG-5′ (SEQ ID NO: 491) MYC-623 Target:5′-CAGGAACTATGACCTCGACTACGACTC-3′ (SEQ ID NO: 818)5′-GAACUAUGACCUCGACUACGACUcg-3′ (SEQ ID NO: 165)3′-UCCUUGAUACUGGAGCUGAUGCUGAGC-5′ (SEQ ID NO: 492) MYC-624 Target:5′-AGGAACTATGACCTCGACTACGACTCG-3′ (SEQ ID NO: 819)5′-AACUAUGACCUCGACUACGACUCgg-3′ (SEQ ID NO: 166)3′-CCUUGAUACUGGAGCUGAUGCUGAGCC-5′ (SEQ ID NO: 493) MYC-625 Target:5′-GGAACTATGACCTCGACTACGACTCGG-3′ (SEQ ID NO: 820)5′-ACUAUGACCUCGACUACGACUCGgt-3′ (SEQ ID NO: 167)3′-CUUGAUACUGGAGCUGAUGCUGAGCCA-5′ (SEQ ID NO: 494) MYC-626 Target:5′-GAACTATGACCTCGACTACGACTCGGT-3′ (SEQ ID NO: 821)5′-CUAUGACCUCGACUACGACUCGGtg-3′ (SEQ ID NO: 168)3′-UUGAUACUGGAGCUGAUGCUGAGCCAC-5′ (SEQ ID NO: 495) MYC-627 Target:5′-AACTATGACCTCGACTACGACTCGGTG-3′ (SEQ ID NO: 822)5′-UAUGACCUCGACUACGACUCGGUgc-3′ (SEQ ID NO: 169)3′-UGAUACUGGAGCUGAUGCUGAGCCACG-5′ (SEQ ID NO: 496) MYC-628 Target:5′-ACTATGACCTCGACTACGACTCGGTGC-3′ (SEQ ID NO: 823)5′-AUGACCUCGACUACGACUCGGUGca-3′ (SEQ ID NO: 170)3′-GAUACUGGAGCUGAUGCUGAGCCACGU-5′ (SEQ ID NO: 497) MYC-629 Target:5′-CTATGACCTCGACTACGACTCGGTGCA-3′ (SEQ ID NO: 824)5′-GAGGAUAUCUGGAAGAAAUUCGAgc-3′ (SEQ ID NO: 171)3′-CGCUCCUAUAGACCUUCUUUAAGCUCG-5′ (SEQ ID NO: 498) MYC-733 Target:5′-GCGAGGATATCTGGAAGAAATTCGAGC-3′ (SEQ ID NO: 825)5′-AGGAUAUCUGGAAGAAAUUCGAGct-3′ (SEQ ID NO: 172)3′-GCUCCUAUAGACCUUCUUUAAGCUCGA-5′ (SEQ ID NO: 499) MYC-734 Target:5′-CGAGGATATCTGGAAGAAATTCGAGCT-3′ (SEQ ID NO: 826)5′-GGAUAUCUGGAAGAAAUUCGAGCtg-3′ (SEQ ID NO: 173)3′-CUCCUAUAGACCUUCUUUAAGCUCGAC-5′ (SEQ ID NO: 500) MYC-735 Target:5′-GAGGATATCTGGAAGAAATTCGAGCTG-3′ (SEQ ID NO: 827)5′-GAUAUCUGGAAGAAAUUCGAGCUgc-3′ (SEQ ID NO: 174)3′-UCCUAUAGACCUUCUUUAAGCUCGACG-5′ (SEQ ID NO: 501) MYC-736 Target:5′-AGGATATCTGGAAGAAATTCGAGCTGC-3′ (SEQ ID NO: 828)5′-AUAUCUGGAAGAAAUUCGAGCUGct-3′ (SEQ ID NO: 175)3′-CCUAUAGACCUUCUUUAAGCUCGACGA-5′ (SEQ ID NO: 502) MYC-737 Target:5′-GGATATCTGGAAGAAATTCGAGCTGCT-3′ (SEQ ID NO: 829)5′-UAUCUGGAAGAAAUUCGAGCUGCtg-3′ (SEQ ID NO: 176)3′-CUAUAGACCUUCUUUAAGCUCGACGAC-5′ (SEQ ID NO: 503) MYC-738 Target:5′-GATATCTGGAAGAAATTCGAGCTGCTG-3′ (SEQ ID NO: 830)5′-AUCUGGAAGAAAUUCGAGCUGCUgc-3′ (SEQ ID NO: 177)3′-UAUAGACCUUCUUUAAGCUCGACGACG-5′ (SEQ ID NO: 504) MYC-739 Target:5′-ATATCTGGAAGAAATTCGAGCTGCTGC-3′ (SEQ ID NO: 831)5′-UCUGGAAGAAAUUCGAGCUGCUGcc-3′ (SEQ ID NO: 178)3′-AUAGACCUUCUUUAAGCUCGACGACGG-5′ (SEQ ID NO: 505) MYC-740 Target:5′-TATCTGGAAGAAATTCGAGCTGCTGCC-3′ (SEQ ID NO: 832)5′-CUGGAAGAAAUUCGAGCUGCUGCcc-3′ (SEQ ID NO: 179)3′-UAGACCUUCUUUAAGCUCGACGACGGG-5′ (SEQ ID NO: 506) MYC-741 Target:5′-ATCTGGAAGAAATTCGAGCTGCTGCCC-3′ (SEQ ID NO: 833)5′-UGGAAGAAAUUCGAGCUGCUGCCca-3′ (SEQ ID NO: 180)3′-AGACCUUCUUUAAGCUCGACGACGGGU-5′ (SEQ ID NO: 507) MYC-742 Target:5′-TCTGGAAGAAATTCGAGCTGCTGCCCA-3′ (SEQ ID NO: 834)5′-GGAAGAAAUUCGAGCUGCUGCCCac-3′ (SEQ ID NO: 181)3′-GACCUUCUUUAAGCUCGACGACGGGUG-5′ (SEQ ID NO: 508) MYC-743 Target:5′-CTGGAAGAAATTCGAGCTGCTGCCCAC-3′ (SEQ ID NO: 835)5′-AGCCGCCGCUCCGGGCUCUGCUCgc-3′ (SEQ ID NO: 182)3′-GAUCGGCGGCGAGGCCCGAGACGAGCG-5′ (SEQ ID NO: 509) MYC-784 Target:5′-CTAGCCGCCGCTCCGGGCTCTGCTCGC-3′ (SEQ ID NO: 836)5′-GCCGCCGCUCCGGGCUCUGCUCGcc-3′ (SEQ ID NO: 183)3′-AUCGGCGGCGAGGCCCGAGACGAGCGG-5′ (SEQ ID NO: 510) MYC-785 Target:5′-TAGCCGCCGCTCCGGGCTCTGCTCGCC-3′ (SEQ ID NO: 837)5′-CCGCCGCUCCGGGCUCUGCUCGCcc-3′ (SEQ ID NO: 184)3′-UCGGCGGCGAGGCCCGAGACGAGCGGG-5′ (SEQ ID NO: 511) MYC-786 Target:5′-AGCCGCCGCTCCGGGCTCTGCTCGCCC-3′ (SEQ ID NO: 838)5′-CGCCGCUCCGGGCUCUGCUCGCCct-3′ (SEQ ID NO: 185)3′-CGGCGGCGAGGCCCGAGACGAGCGGGA-5′ (SEQ ID NO: 512) MYC-787 Target:5′-GCCGCCGCTCCGGGCTCTGCTCGCCCT-3′ (SEQ ID NO: 839)5′-GCCGCUCCGGGCUCUGCUCGCCCtc-3′ (SEQ ID NO: 186)3′-GGCGGCGAGGCCCGAGACGAGCGGGAG-5′ (SEQ ID NO: 513) MYC-788 Target:5′-CCGCCGCTCCGGGCTCTGCTCGCCCTC-3′ (SEQ ID NO: 840)5′-GGAGGAGACAUGGUGAACCAGAGtt-3′ (SEQ ID NO: 187)3′-ACCCUCCUCUGUACCACUUGGUCUCAA-5′ (SEQ ID NO: 514) MYC-913 Target:5′-TGGGAGGAGACATGGTGAACCAGAGTT-3′ (SEQ ID NO: 841)5′-GAGGAGACAUGGUGAACCAGAGUtt-3′ (SEQ ID NO: 188)3′-CCCUCCUCUGUACCACUUGGUCUCAAA-5′ (SEQ ID NO: 515) MYC-914 Target:5′-GGGAGGAGACATGGTGAACCAGAGTTT-3′ (SEQ ID NO: 842)5′-AGGAGACAUGGUGAACCAGAGUUtc-3′ (SEQ ID NO: 189)3′-CCUCCUCUGUACCACUUGGUCUCAAAG-5′ (SEQ ID NO: 516) MYC-915 Target:5′-GGAGGAGACATGGTGAACCAGAGTTTC-3′ (SEQ ID NO: 843)5′-GGAGACAUGGUGAACCAGAGUUUca-3′ (SEQ ID NO: 190)3′-CUCCUCUGUACCACUUGGUCUCAAAGU-5′ (SEQ ID NO: 517) MYC-916 Target:5′-GAGGAGACATGGTGAACCAGAGTTTCA-3′ (SEQ ID NO: 844)5′-GAGACAUGGUGAACCAGAGUUUCat-3′ (SEQ ID NO: 191)3′-UCCUCUGUACCACUUGGUCUCAAAGUA-5′ (SEQ ID NO: 518) MYC-917 Target:5′-AGGAGACATGGTGAACCAGAGTTTCAT-3′ (SEQ ID NO: 845)5′-GACGACGAGACCUUCAUCAAAAAca-3′ (SEQ ID NO: 192)3′-GCCUGCUGCUCUGGAAGUAGUUUUUGU-5′ (SEQ ID NO: 519) MYC-952 Target:5′-CGGACGACGAGACCTTCATCAAAAACA-3′ (SEQ ID NO: 846)5′-ACGACGAGACCUUCAUCAAAAACat-3′ (SEQ ID NO: 193)3′-CCUGCUGCUCUGGAAGUAGUUUUUGUA-5′ (SEQ ID NO: 520) MYC-953 Target:5′-GGACGACGAGACCTTCATCAAAAACAT-3′ (SEQ ID NO: 847)5′-AACAUCAUCAUCCAGGACUGUAUgt-3′ (SEQ ID NO: 194)3′-UUUUGUAGUAGUAGGUCCUGACAUACA-5′ (SEQ ID NO: 521) MYC-973 Target:5′-AAAACATCATCATCCAGGACTGTATGT-3′ (SEQ ID NO: 848)5′-ACAUCAUCAUCCAGGACUGUAUGtg-3′ (SEQ ID NO: 195)3′-UUUGUAGUAGUAGGUCCUGACAUACAC-5′ (SEQ ID NO: 522) MYC-974 Target:5′-AAACATCATCATCCAGGACTGTATGTG-3′ (SEQ ID NO: 849)5′-CAUCAUCAUCCAGGACUGUAUGUgg-3′ (SEQ ID NO: 196)3′-UUGUAGUAGUAGGUCCUGACAUACACC-5′ (SEQ ID NO: 523) MYC-975 Target:5′-AACATCATCATCCAGGACTGTATGTGG-3′ (SEQ ID NO: 850)5′-AUCAUCAUCCAGGACUGUAUGUGga-3′ (SEQ ID NO: 197)3′-UGUAGUAGUAGGUCCUGACAUACACCU-5′ (SEQ ID NO: 524) MYC-976 Target:5′-ACATCATCATCCAGGACTGTATGTGGA-3′ (SEQ ID NO: 851)5′-UCAUCAUCCAGGACUGUAUGUGGag-3′ (SEQ ID NO: 198)3′-GUAGUAGUAGGUCCUGACAUACACCUC-5′ (SEQ ID NO: 525) MYC-977 Target:5′-CATCATCATCCAGGACTGTATGTGGAG-3′ (SEQ ID NO: 852)5′-CAUCAUCCAGGACUGUAUGUGGAgc-3′ (SEQ ID NO: 199)3′-UAGUAGUAGGUCCUGACAUACACCUCG-5′ (SEQ ID NO: 526) MYC-978 Target:5′-ATCATCATCCAGGACTGTATGTGGAGC-3′ (SEQ ID NO: 853)5′-AUCAUCCAGGACUGUAUGUGGAGcg-3′ (SEQ ID NO: 200)3′-AGUAGUAGGUCCUGACAUACACCUCGC-5′ (SEQ ID NO: 527) MYC-979 Target:5′-TCATCATCCAGGACTGTATGTGGAGCG-3′ (SEQ ID NO: 854)5′-UCAUCCAGGACUGUAUGUGGAGCgg-3′ (SEQ ID NO: 201)3′-GUAGUAGGUCCUGACAUACACCUCGCC-5′ (SEQ ID NO: 528) MYC-980 Target:5′-CATCATCCAGGACTGTATGTGGAGCGG-3′ (SEQ ID NO: 855)5′-CAUCCAGGACUGUAUGUGGAGCGgc-3′ (SEQ ID NO: 202)3′-UAGUAGGUCCUGACAUACACCUCGCCG-5′ (SEQ ID NO: 529) MYC-981 Target:5′-ATCATCCAGGACTGTATGTGGAGCGGC-3′ (SEQ ID NO: 856)5′-AUCCAGGACUGUAUGUGGAGCGGct-3′ (SEQ ID NO: 203)3′-AGUAGGUCCUGACAUACACCUCGCCGA-5′ (SEQ ID NO: 530) MYC-982 Target:5′-TCATCCAGGACTGTATGTGGAGCGGCT-3′ (SEQ ID NO: 857)5′-UCCAGGACUGUAUGUGGAGCGGCtt-3′ (SEQ ID NO: 204)3′-GUAGGUCCUGACAUACACCUCGCCGAA-5′ (SEQ ID NO: 531) MYC-983 Target:5′-CATCCAGGACTGTATGTGGAGCGGCTT-3′ (SEQ ID NO: 858)5′-CCAGGACUGUAUGUGGAGCGGCUtc-3′ (SEQ ID NO: 205)3′-UAGGUCCUGACAUACACCUCGCCGAAG-5′ (SEQ ID NO: 532) MYC-984 Target:5′-ATCCAGGACTGTATGTGGAGCGGCTTC-3′ (SEQ ID NO: 859)5′-CAGGACUGUAUGUGGAGCGGCUUct-3′ (SEQ ID NO: 206)3′-AGGUCCUGACAUACACCUCGCCGAAGA-5′ (SEQ ID NO: 533) MYC-985 Target:5′-TCCAGGACTGTATGTGGAGCGGCTTCT-3′ (SEQ ID NO: 860)5′-AGGACUGUAUGUGGAGCGGCUUCtc-3′ (SEQ ID NO: 207)3′-GGUCCUGACAUACACCUCGCCGAAGAG-5′ (SEQ ID NO: 534) MYC-986 Target:5′-CCAGGACTGTATGTGGAGCGGCTTCTC-3′ (SEQ ID NO: 861)5′-GAGAAGCUGGCCUCCUACCAGGCtg-3′ (SEQ ID NO: 208)3′-GUCUCUUCGACCGGAGGAUGGUCCGAC-5′ (SEQ ID NO: 535) MYC-1033 Target:5′-CAGAGAAGCTGGCCTCCTACCAGGCTG-3′ (SEQ ID NO: 862)5′-AGAAGCUGGCCUCCUACCAGGCUgc-3′ (SEQ ID NO: 209)3′-UCUCUUCGACCGGAGGAUGGUCCGACG-5′ (SEQ ID NO: 536) MYC-1034 Target:5′-AGAGAAGCTGGCCTCCTACCAGGCTGC-3′ (SEQ ID NO: 863)5′-GAAGCUGGCCUCCUACCAGGCUGcg-3′ (SEQ ID NO: 210)3′-CUCUUCGACCGGAGGAUGGUCCGACGC-5′ (SEQ ID NO: 537) MYC-1035 Target:5′-GAGAAGCTGGCCTCCTACCAGGCTGCG-3′ (SEQ ID NO: 864)5′-AAGCUGGCCUCCUACCAGGCUGCgc-3′ (SEQ ID NO: 211)3′-UCUUCGACCGGAGGAUGGUCCGACGCG-5′ (SEQ ID NO: 538) MYC-1036 Target:5′-AGAAGCTGGCCTCCTACCAGGCTGCGC-3′ (SEQ ID NO: 865)5′-AGCUGGCCUCCUACCAGGCUGCGcg-3′ (SEQ ID NO: 212)3′-CUUCGACCGGAGGAUGGUCCGACGCGC-5′ (SEQ ID NO: 539) MYC-1037 Target:5′-GAAGCTGGCCTCCTACCAGGCTGCGCG-3′ (SEQ ID NO: 866)5′-GCUGGCCUCCUACCAGGCUGCGCgc-3′ (SEQ ID NO: 213)3′-UUCGACCGGAGGAUGGUCCGACGCGCG-5′ (SEQ ID NO: 540) MYC-1038 Target:5′-AAGCTGGCCTCCTACCAGGCTGCGCGC-3′ (SEQ ID NO: 867)5′-CUGGCCUCCUACCAGGCUGCGCGca-3′ (SEQ ID NO: 214)3′-UCGACCGGAGGAUGGUCCGACGCGCGU-5′ (SEQ ID NO: 541) MYC-1039 Target:5′-AGCTGGCCTCCTACCAGGCTGCGCGCA-3′ (SEQ ID NO: 868)5′-UGGCCUCCUACCAGGCUGCGCGCaa-3′ (SEQ ID NO: 215)3′-CGACCGGAGGAUGGUCCGACGCGCGUU-5′ (SEQ ID NO: 542) MYC-1040 Target:5′-GCTGGCCTCCTACCAGGCTGCGCGCAA-3′ (SEQ ID NO: 869)5′-GGCCUCCUACCAGGCUGCGCGCAaa-3′ (SEQ ID NO: 216)3′-GACCGGAGGAUGGUCCGACGCGCGUUU-5′ (SEQ ID NO: 543) MYC-1041 Target:5′-CTGGCCTCCTACCAGGCTGCGCGCAAA-3′ (SEQ ID NO: 870)5′-GCCUCCUACCAGGCUGCGCGCAAag-3′ (SEQ ID NO: 217)3′-ACCGGAGGAUGGUCCGACGCGCGUUUC-5′ (SEQ ID NO: 544) MYC-1042 Target:5′-TGGCCTCCTACCAGGCTGCGCGCAAAG-3′ (SEQ ID NO: 871)5′-CCUCCUACCAGGCUGCGCGCAAAga-3′ (SEQ ID NO: 218)3′-CCGGAGGAUGGUCCGACGCGCGUUUCU-5′ (SEQ ID NO: 545) MYC-1043 Target:5′-GGCCTCCTACCAGGCTGCGCGCAAAGA-3′ (SEQ ID NO: 872)5′-CUCCUACCAGGCUGCGCGCAAAGac-3′ (SEQ ID NO: 219)3′-CGGAGGAUGGUCCGACGCGCGUUUCUG-5′ (SEQ ID NO: 546) MYC-1044 Target:5′-GCCTCCTACCAGGCTGCGCGCAAAGAC-3′ (SEQ ID NO: 873)5′-UCCUACCAGGCUGCGCGCAAAGAca-3′ (SEQ ID NO: 220)3′-GGAGGAUGGUCCGACGCGCGUUUCUGU-5′ (SEQ ID NO: 547) MYC-1045 Target:5′-CCTCCTACCAGGCTGCGCGCAAAGACA-3′ (SEQ ID NO: 874)5′-CCUACCAGGCUGCGCGCAAAGACag-3′ (SEQ ID NO: 221)3′-GAGGAUGGUCCGACGCGCGUUUCUGUC-5′ (SEQ ID NO: 548) MYC-1046 Target:5′-CTCCTACCAGGCTGCGCGCAAAGACAG-3′ (SEQ ID NO: 875)5′-CUACCAGGCUGCGCGCAAAGACAgc-3′ (SEQ ID NO: 222)3′-AGGAUGGUCCGACGCGCGUUUCUGUCG-5′ (SEQ ID NO: 549) MYC-1047 Target:5′-TCCTACCAGGCTGCGCGCAAAGACAGC-3′ (SEQ ID NO: 876)5′-UACCAGGCUGCGCGCAAAGACAGcg-3′ (SEQ ID NO: 223)3′-GGAUGGUCCGACGCGCGUUUCUGUCGC-5′ (SEQ ID NO: 550) MYC-1048 Target:5′-CCTACCAGGCTGCGCGCAAAGACAGCG-3′ (SEQ ID NO: 877)5′-ACCAGGCUGCGCGCAAAGACAGCgg-3′ (SEQ ID NO: 224)3′-GAUGGUCCGACGCGCGUUUCUGUCGCC-5′ (SEQ ID NO: 551) MYC-1049 Target:5′-CTACCAGGCTGCGCGCAAAGACAGCGG-3′ (SEQ ID NO: 878)5′-CCAGGCUGCGCGCAAAGACAGCGgc-3′ (SEQ ID NO: 225)3′-AUGGUCCGACGCGCGUUUCUGUCGCCG-5′ (SEQ ID NO: 552) MYC-1050 Target:5′-TACCAGGCTGCGCGCAAAGACAGCGGC-3′ (SEQ ID NO: 879)5′-CAGGCUGCGCGCAAAGACAGCGGca-3′ (SEQ ID NO: 226)3′-UGGUCCGACGCGCGUUUCUGUCGCCGU-5′ (SEQ ID NO: 553) MYC-1051 Target:5′-ACCAGGCTGCGCGCAAAGACAGCGGCA-3′ (SEQ ID NO: 880)5′-AGGCUGCGCGCAAAGACAGCGGCag-3′ (SEQ ID NO: 227)3′-GGUCCGACGCGCGUUUCUGUCGCCGUC-5′ (SEQ ID NO: 554) MYC-1052 Target:5′-CCAGGCTGCGCGCAAAGACAGCGGCAG-3′ (SEQ ID NO: 881)5′-GGCUGCGCGCAAAGACAGCGGCAgc-3′ (SEQ ID NO: 228)3′-GUCCGACGCGCGUUUCUGUCGCCGUCG-5′ (SEQ ID NO: 555) MYC-1053 Target:5′-CAGGCTGCGCGCAAAGACAGCGGCAGC-3′ (SEQ ID NO: 882)5′-CACAGCGUCUGCUCCACCUCCAGct-3′ (SEQ ID NO: 229)3′-CGGUGUCGCAGACGAGGUGGAGGUCGA-5′ (SEQ ID NO: 556) MYC-1096 Target:5′-GCCACAGCGTCTGCTCCACCTCCAGCT-3′ (SEQ ID NO: 883)5′-ACAGCGUCUGCUCCACCUCCAGCtt-3′ (SEQ ID NO: 230)3′-GGUGUCGCAGACGAGGUGGAGGUCGAA-5′ (SEQ ID NO: 557) MYC-1097 Target:5′-CCACAGCGTCTGCTCCACCTCCAGCTT-3′ (SEQ ID NO: 884)5′-CAGCGUCUGCUCCACCUCCAGCUtg-3′ (SEQ ID NO: 231)3′-GUGUCGCAGACGAGGUGGAGGUCGAAC-5′ (SEQ ID NO: 558) MYC-1098 Target:5′-CACAGCGTCTGCTCCACCTCCAGCTTG-3′ (SEQ ID NO: 885)5′-AGCGUCUGCUCCACCUCCAGCUUgt-3′ (SEQ ID NO: 232)3′-UGUCGCAGACGAGGUGGAGGUCGAACA-5′ (SEQ ID NO: 559) MYC-1099 Target:5′-ACAGCGTCTGCTCCACCTCCAGCTTGT-3′ (SEQ ID NO: 886)5′-GCGUCUGCUCCACCUCCAGCUUGta-3′ (SEQ ID NO: 233)3′-GUCGCAGACGAGGUGGAGGUCGAACAU-5′ (SEQ ID NO: 560) MYC-1100 Target:5′-CAGCGTCTGCTCCACCTCCAGCTTGTA-3′ (SEQ ID NO: 887)5′-CGUCUGCUCCACCUCCAGCUUGUac-3′ (SEQ ID NO: 234)3′-UCGCAGACGAGGUGGAGGUCGAACAUG-5′ (SEQ ID NO: 561) MYC-1101 Target:5′-AGCGTCTGCTCCACCTCCAGCTTGTAC-3′ (SEQ ID NO: 888)5′-CUCAACGACAGCAGCUCGCCCAAgt-3′ (SEQ ID NO: 235)3′-GAGAGUUGCUGUCGUCGAGCGGGUUCA-5′ (SEQ ID NO: 562) MYC-1189 Target:5′-CTCTCAACGACAGCAGCTCGCCCAAGT-3′ (SEQ ID NO: 889)5′-UCAACGACAGCAGCUCGCCCAAGtc-3′ (SEQ ID NO: 236)3′-AGAGUUGCUGUCGUCGAGCGGGUUCAG-5′ (SEQ ID NO: 563) MYC-1190 Target:5′-TCTCAACGACAGCAGCTCGCCCAAGTC-3′ (SEQ ID NO: 890)5′-CAACGACAGCAGCUCGCCCAAGUcc-3′ (SEQ ID NO: 237)3′-GAGUUGCUGUCGUCGAGCGGGUUCAGG-5′ (SEQ ID NO: 564) MYC-1191 Target:5′-CTCAACGACAGCAGCTCGCCCAAGTCC-3′ (SEQ ID NO: 891)5′-AACGACAGCAGCUCGCCCAAGUCct-3′ (SEQ ID NO: 238)3′-AGUUGCUGUCGUCGAGCGGGUUCAGGA-5′ (SEQ ID NO: 565) MYC-1192 Target:5′-TCAACGACAGCAGCTCGCCCAAGTCCT-3′ (SEQ ID NO: 892)5′-ACGACAGCAGCUCGCCCAAGUCCtg-3′ (SEQ ID NO: 239)3′-GUUGCUGUCGUCGAGCGGGUUCAGGAC-5′ (SEQ ID NO: 566) MYC-1193 Target:5′-CAACGACAGCAGCTCGCCCAAGTCCTG-3′ (SEQ ID NO: 893)5′-CAUGAGGAGACACCGCCCACCACca-3′ (SEQ ID NO: 240)3′-AGGUACUCCUCUGUGGCGGGUGGUGGU-5′ (SEQ ID NO: 567) MYC-1315 Target:5′-TCCATGAGGAGACACCGCCCACCACCA-3′ (SEQ ID NO: 894)5′-AUGAGGAGACACCGCCCACCACCag-3′ (SEQ ID NO: 241)3′-GGUACUCCUCUGUGGCGGGUGGUGGUC-5′ (SEQ ID NO: 568) MYC-1316 Target:5′-CCATGAGGAGACACCGCCCACCACCAG-3′ (SEQ ID NO: 895)5′-UGAGGAGACACCGCCCACCACCAgc-3′ (SEQ ID NO: 242)3′-GUACUCCUCUGUGGCGGGUGGUGGUCG-5′ (SEQ ID NO: 569) MYC-1317 Target:5′-CATGAGGAGACACCGCCCACCACCAGC-3′ (SEQ ID NO: 896)5′-GAGGAGACACCGCCCACCACCAGca-3′ (SEQ ID NO: 243)3′-UACUCCUCUGUGGCGGGUGGUGGUCGU-5′ (SEQ ID NO: 570) MYC-1318 Target:5′-ATGAGGAGACACCGCCCACCACCAGCA-3′ (SEQ ID NO: 897)5′-AGGAGACACCGCCCACCACCAGCag-3′ (SEQ ID NO: 244)3′-ACUCCUCUGUGGCGGGUGGUGGUCGUC-5′ (SEQ ID NO: 571) MYC-1319 Target:5′-TGAGGAGACACCGCCCACCACCAGCAG-3′ (SEQ ID NO: 898)5′-GGAGACACCGCCCACCACCAGCAgc-3′ (SEQ ID NO: 245)3′-CUCCUCUGUGGCGGGUGGUGGUCGUCG-5′ (SEQ ID NO: 572) MYC-1320 Target:5′-GAGGAGACACCGCCCACCACCAGCAGC-3′ (SEQ ID NO: 899)5′-GAGACACCGCCCACCACCAGCAGcg-3′ (SEQ ID NO: 246)3′-UCCUCUGUGGCGGGUGGUGGUCGUCGC-5′ (SEQ ID NO: 573) MYC-1321 Target:5′-AGGAGACACCGCCCACCACCAGCAGCG-3′ (SEQ ID NO: 900)5′-AGACACCGCCCACCACCAGCAGCga-3′ (SEQ ID NO: 247)3′-CCUCUGUGGCGGGUGGUGGUCGUCGCU-5′ (SEQ ID NO: 574) MYC-1322 Target:5′-GGAGACACCGCCCACCACCAGCAGCGA-3′ (SEQ ID NO: 901)5′-GACACCGCCCACCACCAGCAGCGac-3′ (SEQ ID NO: 248)3′-CUCUGUGGCGGGUGGUGGUCGUCGCUG-5′ (SEQ ID NO: 575) MYC-1323 Target:5′-GAGACACCGCCCACCACCAGCAGCGAC-3′ (SEQ ID NO: 902)5′-ACACCGCCCACCACCAGCAGCGAct-3′ (SEQ ID NO: 249)3′-UCUGUGGCGGGUGGUGGUCGUCGCUGA-5′ (SEQ ID NO: 576) MYC-1324 Target:5′-AGACACCGCCCACCACCAGCAGCGACT-3′ (SEQ ID NO: 903)5′-CACCGCCCACCACCAGCAGCGACtc-3′ (SEQ ID NO: 250)3′-CUGUGGCGGGUGGUGGUCGUCGCUGAG-5′ (SEQ ID NO: 577) MYC-1325 Target:5′-GACACCGCCCACCACCAGCAGCGACTC-3′ (SEQ ID NO: 904)5′-ACCGCCCACCACCAGCAGCGACUct-3′ (SEQ ID NO: 251)3′-UGUGGCGGGUGGUGGUCGUCGCUGAGA-5′ (SEQ ID NO: 578) MYC-1326 Target:5′-ACACCGCCCACCACCAGCAGCGACTCT-3′ (SEQ ID NO: 905)5′-CCGCCCACCACCAGCAGCGACUCtg-3′ (SEQ ID NO: 252)3′-GUGGCGGGUGGUGGUCGUCGCUGAGAC-5′ (SEQ ID NO: 579) MYC-1327 Target:5′-CACCGCCCACCACCAGCAGCGACTCTG-3′ (SEQ ID NO: 906)5′-CGCCCACCACCAGCAGCGACUCUga-3′ (SEQ ID NO: 253)3′-UGGCGGGUGGUGGUCGUCGCUGAGACU-5′ (SEQ ID NO: 580) MYC-1328 Target:5′-ACCGCCCACCACCAGCAGCGACTCTGA-3′ (SEQ ID NO: 907)5′-GCCCACCACCAGCAGCGACUCUGag-3′ (SEQ ID NO: 254)3′-GGCGGGUGGUGGUCGUCGCUGAGACUC-5′ (SEQ ID NO: 581) MYC-1329 Target:5′-CCGCCCACCACCAGCAGCGACTCTGAG-3′ (SEQ ID NO: 908)5′-CCCACCACCAGCAGCGACUCUGAgg-3′ (SEQ ID NO: 255)3′-GCGGGUGGUGGUCGUCGCUGAGACUCC-5′ (SEQ ID NO: 582) MYC-1330 Target:5′-CGCCCACCACCAGCAGCGACTCTGAGG-3′ (SEQ ID NO: 909)5′-CCACCACCAGCAGCGACUCUGAGga-3′ (SEQ ID NO: 256)3′-CGGGUGGUGGUCGUCGCUGAGACUCCU-5′ (SEQ ID NO: 583) MYC-1331 Target:5′-GCCCACCACCAGCAGCGACTCTGAGGA-3′ (SEQ ID NO: 910)5′-CACCACCAGCAGCGACUCUGAGGag-3′ (SEQ ID NO: 257)3′-GGGUGGUGGUCGUCGCUGAGACUCCUC-5′ (SEQ ID NO: 584) MYC-1332 Target:5′-CCCACCACCAGCAGCGACTCTGAGGAG-3′ (SEQ ID NO: 911)5′-ACCACCAGCAGCGACUCUGAGGAgg-3′ (SEQ ID NO: 258)3′-GGUGGUGGUCGUCGCUGAGACUCCUCC-5′ (SEQ ID NO: 585) MYC-1333 Target:5′-CCACCACCAGCAGCGACTCTGAGGAGG-3′ (SEQ ID NO: 912)5′-CCACCAGCAGCGACUCUGAGGAGga-3′ (SEQ ID NO: 259)3′-GUGGUGGUCGUCGCUGAGACUCCUCCU-5′ (SEQ ID NO: 586) MYC-1334 Target:5′-CACCACCAGCAGCGACTCTGAGGAGGA-3′ (SEQ ID NO: 913)5′-CAAGAAGAUGAGGAAGAAAUCGAtg-3′ (SEQ ID NO: 260)3′-UUGUUCUUCUACUCCUUCUUUAGCUAC-5′ (SEQ ID NO: 587) MYC-1360 Target:5′-AACAAGAAGATGAGGAAGAAATCGATG-3′ (SEQ ID NO: 914)5′-AAGAAGAUGAGGAAGAAAUCGAUgt-3′ (SEQ ID NO: 261)3′-UGUUCUUCUACUCCUUCUUUAGCUACA-5′ (SEQ ID NO: 588) MYC-1361 Target:5′-ACAAGAAGATGAGGAAGAAATCGATGT-3′ (SEQ ID NO: 915)5′-GAGGCCACAGCAAACCUCCUCACag-3′ (SEQ ID NO: 262)3′-ACCUCCGGUGUCGUUUGGAGGAGUGUC-5′ (SEQ ID NO: 589) MYC-1448 Target:5′-TGGAGGCCACAGCAAACCTCCTCACAG-3′ (SEQ ID NO: 916)5′-CACAGCCCACUGGUCCUCAAGAGgt-3′ (SEQ ID NO: 263)3′-GAGUGUCGGGUGACCAGGAGUUCUCCA-5′ (SEQ ID NO: 590) MYC-1468 Target:5′-CTCACAGCCCACTGGTCCTCAAGAGGT-3′ (SEQ ID NO: 917)5′-ACAGCCCACUGGUCCUCAAGAGGtg-3′ (SEQ ID NO: 264)3′-AGUGUCGGGUGACCAGGAGUUCUCCAC-5′ (SEQ ID NO: 591) MYC-1469 Target:5′-TCACAGCCCACTGGTCCTCAAGAGGTG-3′ (SEQ ID NO: 918)5′-CAGCCCACUGGUCCUCAAGAGGUgc-3′ (SEQ ID NO: 265)3′-GUGUCGGGUGACCAGGAGUUCUCCACG-5′ (SEQ ID NO: 592) MYC-1470 Target:5′-CACAGCCCACTGGTCCTCAAGAGGTGC-3′ (SEQ ID NO: 919)5′-AGCCCACUGGUCCUCAAGAGGUGcc-3′ (SEQ ID NO: 266)3′-UGUCGGGUGACCAGGAGUUCUCCACGG-5′ (SEQ ID NO: 593) MYC-1471 Target:5′-ACAGCCCACTGGTCCTCAAGAGGTGCC-3′ (SEQ ID NO: 920)5′-GCCCACUGGUCCUCAAGAGGUGCca-3′ (SEQ ID NO: 267)3′-GUCGGGUGACCAGGAGUUCUCCACGGU-5′ (SEQ ID NO: 594) MYC-1472 Target:5′-CAGCCCACTGGTCCTCAAGAGGTGCCA-3′ (SEQ ID NO: 921)5′-CCCACUGGUCCUCAAGAGGUGCCac-3′ (SEQ ID NO: 268)3′-UCGGGUGACCAGGAGUUCUCCACGGUG-5′ (SEQ ID NO: 595) MYC-1473 Target:5′-AGCCCACTGGTCCTCAAGAGGTGCCAC-3′ (SEQ ID NO: 922)5′-CCACUGGUCCUCAAGAGGUGCCAcg-3′ (SEQ ID NO: 269)3′-CGGGUGACCAGGAGUUCUCCACGGUGC-5′ (SEQ ID NO: 596) MYC-1474 Target:5′-GCCCACTGGTCCTCAAGAGGTGCCACG-3′ (SEQ ID NO: 923)5′-CACUGGUCCUCAAGAGGUGCCACgt-3′ (SEQ ID NO: 270)3′-GGGUGACCAGGAGUUCUCCACGGUGCA-5′ (SEQ ID NO: 597) MYC-1475 Target:5′-CCCACTGGTCCTCAAGAGGTGCCACGT-3′ (SEQ ID NO: 924)5′-ACUGGUCCUCAAGAGGUGCCACGtc-3′ (SEQ ID NO: 271)3′-GGUGACCAGGAGUUCUCCACGGUGCAG-5′ (SEQ ID NO: 598) MYC-1476 Target:5′-CCACTGGTCCTCAAGAGGTGCCACGTC-3′ (SEQ ID NO: 925)5′-CUGGUCCUCAAGAGGUGCCACGUct-3′ (SEQ ID NO: 272)3′-GUGACCAGGAGUUCUCCACGGUGCAGA-5′ (SEQ ID NO: 599) MYC-1477 Target:5′-CACTGGTCCTCAAGAGGTGCCACGTCT-3′ (SEQ ID NO: 926)5′-UGGUCCUCAAGAGGUGCCACGUCtc-3′ (SEQ ID NO: 273)3′-UGACCAGGAGUUCUCCACGGUGCAGAG-5′ (SEQ ID NO: 600) MYC-1478 Target:5′-ACTGGTCCTCAAGAGGTGCCACGTCTC-3′ (SEQ ID NO: 927)5′-GGUCCUCAAGAGGUGCCACGUCUcc-3′ (SEQ ID NO: 274)3′-GACCAGGAGUUCUCCACGGUGCAGAGG-5′ (SEQ ID NO: 601) MYC-1479 Target:5′-CTGGTCCTCAAGAGGTGCCACGTCTCC-3′ (SEQ ID NO: 928)5′-GUCCUCAAGAGGUGCCACGUCUCca-3′ (SEQ ID NO: 275)3′-ACCAGGAGUUCUCCACGGUGCAGAGGU-5′ (SEQ ID NO: 602) MYC-1480 Target:5′-TGGTCCTCAAGAGGTGCCACGTCTCCA-3′ (SEQ ID NO: 929)5′-UCCUCAAGAGGUGCCACGUCUCCac-3′ (SEQ ID NO: 276)3′-CCAGGAGUUCUCCACGGUGCAGAGGUG-5′ (SEQ ID NO: 603) MYC-1481 Target:5′-GGTCCTCAAGAGGTGCCACGTCTCCAC-3′ (SEQ ID NO: 930)5′-CCUCAAGAGGUGCCACGUCUCCAca-3′ (SEQ ID NO: 277)3′-CAGGAGUUCUCCACGGUGCAGAGGUGU-5′ (SEQ ID NO: 604) MYC-1482 Target:5′-GTCCTCAAGAGGTGCCACGTCTCCACA-3′ (SEQ ID NO: 931)5′-CUCAAGAGGUGCCACGUCUCCACac-3′ (SEQ ID NO: 278)3′-AGGAGUUCUCCACGGUGCAGAGGUGUG-5′ (SEQ ID NO: 605) MYC-1483 Target:5′-TCCTCAAGAGGTGCCACGTCTCCACAC-3′ (SEQ ID NO: 932)5′-AGCUUUUUUGCCCUGCGUGACCAga-3′ (SEQ ID NO: 279)3′-CCUCGAAAAAACGGGACGCACUGGUCU-5′ (SEQ ID NO: 606) MYC-1711 Target:5′-GGAGCTTTTTTGCCCTGCGTGACCAGA-3′ (SEQ ID NO: 933)5′-GCUUUUUUGCCCUGCGUGACCAGat-3′ (SEQ ID NO: 280)3′-CUCGAAAAAACGGGACGCACUGGUCUA-5′ (SEQ ID NO: 607) MYC-1712 Target:5′-GAGCTTTTTTGCCCTGCGTGACCAGAT-3′ (SEQ ID NO: 934)5′-CUUUUUUGCCCUGCGUGACCAGAtc-3′ (SEQ ID NO: 281)3′-UCGAAAAAACGGGACGCACUGGUCUAG-5′ (SEQ ID NO: 608) MYC-1713 Target:5′-AGCTTTTTTGCCCTGCGTGACCAGATC-3′ (SEQ ID NO: 935)5′-UUUUUUGCCCUGCGUGACCAGAUcc-3′ (SEQ ID NO: 282)3′-CGAAAAAACGGGACGCACUGGUCUAGG-5′ (SEQ ID NO: 609) MYC-1714 Target:5′-GCTTTTTTGCCCTGCGTGACCAGATCC-3′ (SEQ ID NO: 936)5′-UUUUUGCCCUGCGUGACCAGAUCcc-3′ (SEQ ID NO: 283)3′-GAAAAAACGGGACGCACUGGUCUAGGG-5′ (SEQ ID NO: 610) MYC-1715 Target:5′-CTTTTTTGCCCTGCGTGACCAGATCCC-3′ (SEQ ID NO: 937)5′-UUUUGCCCUGCGUGACCAGAUCCcg-3′ (SEQ ID NO: 284)3′-AAAAAACGGGACGCACUGGUCUAGGGC-5′ (SEQ ID NO: 611) MYC-1716 Target:5′-TTTTTTGCCCTGCGTGACCAGATCCCG-3′ (SEQ ID NO: 938)5′-UUUGCCCUGCGUGACCAGAUCCCgg-3′ (SEQ ID NO: 285)3′-AAAAACGGGACGCACUGGUCUAGGGCC-5′ (SEQ ID NO: 612) MYC-1717 Target:5′-TTTTTGCCCTGCGTGACCAGATCCCGG-3′ (SEQ ID NO: 939)5′-UUGCCCUGCGUGACCAGAUCCCGga-3′ (SEQ ID NO: 286)3′-AAAACGGGACGCACUGGUCUAGGGCCU-5′ (SEQ ID NO: 613) MYC-1718 Target:5′-TTTTGCCCTGCGTGACCAGATCCCGGA-3′ (SEQ ID NO: 940)5′-UGCCCUGCGUGACCAGAUCCCGGag-3′ (SEQ ID NO: 287)3′-AAACGGGACGCACUGGUCUAGGGCCUC-5′ (SEQ ID NO: 614) MYC-1719 Target:5′-TTTGCCCTGCGTGACCAGATCCCGGAG-3′ (SEQ ID NO: 941)5′-GCCCUGCGUGACCAGAUCCCGGAgt-3′ (SEQ ID NO: 288)3′-AACGGGACGCACUGGUCUAGGGCCUCA-5′ (SEQ ID NO: 615) MYC-1720 Target:5′-TTGCCCTGCGTGACCAGATCCCGGAGT-3′ (SEQ ID NO: 942)5′-CCCUGCGUGACCAGAUCCCGGAGtt-3′ (SEQ ID NO: 289)3′-ACGGGACGCACUGGUCUAGGGCCUCAA-5′ (SEQ ID NO: 616) MYC-1721 Target:5′-TGCCCTGCGTGACCAGATCCCGGAGTT-3′ (SEQ ID NO: 943)5′-GGAAACGACGAGAACAGUUGAAAca-3′ (SEQ ID NO: 290)3′-CGCCUUUGCUGCUCUUGUCAACUUUGU-5′ (SEQ ID NO: 617) MYC-1856 Target:5′-GCGGAAACGACGAGAACAGTTGAAACA-3′ (SEQ ID NO: 944)5′-GAAACGACGAGAACAGUUGAAACac-3′ (SEQ ID NO: 291)3′-GCCUUUGCUGCUCUUGUCAACUUUGUG-5′ (SEQ ID NO: 618) MYC-1857 Target:5′-CGGAAACGACGAGAACAGTTGAAACAC-3′ (SEQ ID NO: 945)5′-UUUAACAGAUUUGUAUUUAAGAAtt-3′ (SEQ ID NO: 292)3′-AGAAAUUGUCUAAACAUAAAUUCUUAA-5′ (SEQ ID NO: 619) MYC-2115 Target:5′-TCTTTAACAGATTTGTATTTAAGAATT-3′ (SEQ ID NO: 946)5′-UUAACAGAUUUGUAUUUAAGAAUtg-3′ (SEQ ID NO: 293)3′-GAAAUUGUCUAAACAUAAAUUCUUAAC-5′ (SEQ ID NO: 620) MYC-2116 Target:5′-CTTTAACAGATTTGTATTTAAGAATTG-3′ (SEQ ID NO: 947)5′-AAAUGUAAAUAACUUUAAUAAAAcg-3′ (SEQ ID NO: 294)3′-AAUUUACAUUUAUUGAAAUUAUUUUGC-5′ (SEQ ID NO: 621) MYC-2193 Target:5′-TTAAATGTAAATAACTTTAATAAAACG-3′ (SEQ ID NO: 948)5′-AAUGUAAAUAACUUUAAUAAAACgt-3′ (SEQ ID NO: 295)3′-AUUUACAUUUAUUGAAAUUAUUUUGCA-5′ (SEQ ID NO: 622) MYC-2194 Target:5′-TAAATGTAAATAACTTTAATAAAACGT-3′ (SEQ ID NO: 949)5′-AUGUAAAUAACUUUAAUAAAACGtt-3′ (SEQ ID NO: 296)3′-UUUACAUUUAUUGAAAUUAUUUUGCAA-5′ (SEQ ID NO: 623) MYC-2195 Target:5′-AAATGTAAATAACTTTAATAAAACGTT-3′ (SEQ ID NO: 950)5′-UGUAAAUAACUUUAAUAAAACGUtt-3′ (SEQ ID NO: 297)3′-UUACAUUUAUUGAAAUUAUUUUGCAAA-5′ (SEQ ID NO: 624) MYC-2196 Target:5′-AATGTAAATAACTTTAATAAAACGTTT-3′ (SEQ ID NO: 951)5′-GUAAAUAACUUUAAUAAAACGUUta-3′ (SEQ ID NO: 298)3′-UACAUUUAUUGAAAUUAUUUUGCAAAU-5′ (SEQ ID NO: 625) MYC-2197 Target:5′-ATGTAAATAACTTTAATAAAACGTTTA-3′ (SEQ ID NO: 952)5′-UAAAUAACUUUAAUAAAACGUUUat-3′ (SEQ ID NO: 299)3′-ACAUUUAUUGAAAUUAUUUUGCAAAUA-5′ (SEQ ID NO: 626) MYC-2198 Target:5′-TGTAAATAACTTTAATAAAACGTTTAT-3′ (SEQ ID NO: 953)5′-AAAUAACUUUAAUAAAACGUUUAta-3′ (SEQ ID NO: 300)3′-CAUUUAUUGAAAUUAUUUUGCAAAUAU-5′ (SEQ ID NO: 627) MYC-2199 Target:5′-GTAAATAACTTTAATAAAACGTTTATA-3′ (SEQ ID NO: 954)5′-AAUAACUUUAAUAAAACGUUUAUag-3′ (SEQ ID NO: 301)3′-AUUUAUUGAAAUUAUUUUGCAAAUAUC-5′ (SEQ ID NO: 628) MYC-2200 Target:5′-TAAATAACTTTAATAAAACGTTTATAG-3′ (SEQ ID NO: 955)5′-AUAACUUUAAUAAAACGUUUAUAgc-3′ (SEQ ID NO: 302)3′-UUUAUUGAAAUUAUUUUGCAAAUAUCG-5′ (SEQ ID NO: 629) MYC-2201 Target:5′-AAATAACTTTAATAAAACGTTTATAGC-3′ (SEQ ID NO: 956)5′-UAACUUUAAUAAAACGUUUAUAGca-3′ (SEQ ID NO: 303)3′-UUAUUGAAAUUAUUUUGCAAAUAUCGU-5′ (SEQ ID NO: 630) MYC-2202 Target:5′-AATAACTTTAATAAAACGTTTATAGCA-3′ (SEQ ID NO: 957)5′-AACUUUAAUAAAACGUUUAUAGCag-3′ (SEQ ID NO: 304)3′-UAUUGAAAUUAUUUUGCAAAUAUCGUC-5′ (SEQ ID NO: 631) MYC-2203 Target:5′-ATAACTTTAATAAAACGTTTATAGCAG-3′ (SEQ ID NO: 958)5′-ACUUUAAUAAAACGUUUAUAGCAgt-3′ (SEQ ID NO: 305)3′-AUUGAAAUUAUUUUGCAAAUAUCGUCA-5′ (SEQ ID NO: 632) MYC-2204 Target:5′-TAACTTTAATAAAACGTTTATAGCAGT-3′ (SEQ ID NO: 959)5′-CUUUAAUAAAACGUUUAUAGCAGtt-3′ (SEQ ID NO: 306)3′-UUGAAAUUAUUUUGCAAAUAUCGUCAA-5′ (SEQ ID NO: 633) MYC-2205 Target:5′-AACTTTAATAAAACGTTTATAGCAGTT-3′ (SEQ ID NO: 960)5′-UUUUUAAAGUUGAUUUUUUUCUAtt-3′ (SEQ ID NO: 307)3′-CGAAAAAUUUCAACUAAAAAAAGAUAA-5′ (SEQ ID NO: 634) MYC-2313 Target:5′-GCTTTTTAAAGTTGATTTTTTTCTATT-3′ (SEQ ID NO: 961)5′-UUUUAAAGUUGAUUUUUUUCUAUtg-3′ (SEQ ID NO: 308)3′-GAAAAAUUUCAACUAAAAAAAGAUAAC-5′ (SEQ ID NO: 635) MYC-2314 Target:5′-CTTTTTAAAGTTGATTTTTTTCTATTG-3′ (SEQ ID NO: 962)5′-UUUAAAGUUGAUUUUUUUCUAUUgt-3′ (SEQ ID NO: 309)3′-AAAAAUUUCAACUAAAAAAAGAUAACA-5′ (SEQ ID NO: 636) MYC-2315 Target:5′-TTTTTAAAGTTGATTTTTTTCTATTGT-3′ (SEQ ID NO: 963)5′-UUAAAGUUGAUUUUUUUCUAUUGtt-3′ (SEQ ID NO: 310)3′-AAAAUUUCAACUAAAAAAAGAUAACAA-5′ (SEQ ID NO: 637) MYC-2316 Target:5′-TTTTAAAGTTGATTTTTTTCTATTGTT-3′ (SEQ ID NO: 964)5′-UAAAGUUGAUUUUUUUCUAUUGUtt-3′ (SEQ ID NO: 311)3′-AAAUUUCAACUAAAAAAAGAUAACAAA-5′ (SEQ ID NO: 638) MYC-2317 Target:5′-TTTAAAGTTGATTTTTTTCTATTGTTT-3′ (SEQ ID NO: 965)5′-AAAGUUGAUUUUUUUCUAUUGUUtt-3′ (SEQ ID NO: 312)3′-AAUUUCAACUAAAAAAAGAUAACAAAA-5′ (SEQ ID NO: 639) MYC-2318 Target:5′-TTAAAGTTGATTTTTTTCTATTGTTTT-3′ (SEQ ID NO: 966)5′-AAGUUGAUUUUUUUCUAUUGUUUtt-3′ (SEQ ID NO: 313)3′-AUUUCAACUAAAAAAAGAUAACAAAAA-5′ (SEQ ID NO: 640) MYC-2319 Target:5′-TAAAGTTGATTTTTTTCTATTGTTTTT-3′ (SEQ ID NO: 967)5′-AGUUGAUUUUUUUCUAUUGUUUUta-3′ (SEQ ID NO: 314)3′-UUUCAACUAAAAAAAGAUAACAAAAAU-5′ (SEQ ID NO: 641) MYC-2320 Target:5′-AAAGTTGATTTTTTTCTATTGTTTTTA-3′ (SEQ ID NO: 968)5′-GUUGAUUUUUUUCUAUUGUUUUUag-3′ (SEQ ID NO: 315)3′-UUCAACUAAAAAAAGAUAACAAAAAUC-5′ (SEQ ID NO: 642) MYC-2321 Target:5′-AAGTTGATTTTTTTCTATTGTTTTTAG-3′ (SEQ ID NO: 969)5′-UUGAUUUUUUUCUAUUGUUUUUAga-3′ (SEQ ID NO: 316)3′-UCAACUAAAAAAAGAUAACAAAAAUCU-5′ (SEQ ID NO: 643) MYC-2322 Target:5′-AGTTGATTTTTTTCTATTGTTTTTAGA-3′ (SEQ ID NO: 970)5′-UGAUUUUUUUCUAUUGUUUUUAGaa-3′ (SEQ ID NO: 317)3′-CAACUAAAAAAAGAUAACAAAAAUCUU-5′ (SEQ ID NO: 644) MYC-2323 Target:5′-GTTGATTTTTTTCTATTGTTTTTAGAA-3′ (SEQ ID NO: 971)5′-GAUUUUUUUCUAUUGUUUUUAGAaa-3′ (SEQ ID NO: 318)3′-AACUAAAAAAAGAUAACAAAAAUCUUU-5′ (SEQ ID NO: 645) MYC-2324 Target:5′-TTGATTTTTTTCTATTGTTTTTAGAAA-3′ (SEQ ID NO: 972)5′-AUUUUUUUCUAUUGUUUUUAGAAaa-3′ (SEQ ID NO: 319)3′-ACUAAAAAAAGAUAACAAAAAUCUUUU-5′ (SEQ ID NO: 646) MYC-2325 Target:5′-TGATTTTTTTCTATTGTTTTTAGAAAA-3′ (SEQ ID NO: 973)5′-UUUUUUUCUAUUGUUUUUAGAAAaa-3′ (SEQ ID NO: 320)3′-CUAAAAAAAGAUAACAAAAAUCUUUUU-5′ (SEQ ID NO: 647) MYC-2326 Target:5′-GATTTTTTTCTATTGTTTTTAGAAAAA-3′ (SEQ ID NO: 974)5′-UUUUUUCUAUUGUUUUUAGAAAAaa-3′ (SEQ ID NO: 321)3′-UAAAAAAAGAUAACAAAAAUCUUUUUU-5′ (SEQ ID NO: 648) MYC-2327 Target:5′-ATTTTTTTCTATTGTTTTTAGAAAAAA-3′ (SEQ ID NO: 975)5′-UUUUUCUAUUGUUUUUAGAAAAAat-3′ (SEQ ID NO: 322)3′-AAAAAAAGAUAACAAAAAUCUUUUUUA-5′ (SEQ ID NO: 649) MYC-2328 Target:5′-TTTTTTTCTATTGTTTTTAGAAAAAAT-3′ (SEQ ID NO: 976)5′-UUUUCUAUUGUUUUUAGAAAAAAta-3′ (SEQ ID NO: 323)3′-AAAAAAGAUAACAAAAAUCUUUUUUAU-5′ (SEQ ID NO: 650) MYC-2329 Target:5′-TTTTTTCTATTGTTTTTAGAAAAAATA-3′ (SEQ ID NO: 977)5′-UUUCUAUUGUUUUUAGAAAAAAUaa-3′ (SEQ ID NO: 324)3′-AAAAAGAUAACAAAAAUCUUUUUUAUU-5′ (SEQ ID NO: 651) MYC-2330 Target:5′-TTTTTCTATTGTTTTTAGAAAAAATAA-3′ (SEQ ID NO: 978)5′-UUCUAUUGUUUUUAGAAAAAAUAaa-3′ (SEQ ID NO: 325)3′-AAAAGAUAACAAAAAUCUUUUUUAUUU-5′ (SEQ ID NO: 652) MYC-2331 Target:5′-TTTTCTATTGTTTTTAGAAAAAATAAA-3′ (SEQ ID NO: 979)5′-UCUAUUGUUUUUAGAAAAAAUAAaa-3′ (SEQ ID NO: 326)3′-AAAGAUAACAAAAAUCUUUUUUAUUUU-5′ (SEQ ID NO: 653) MYC-2332 Target:5′-TTTCTATTGTTTTTAGAAAAAATAAAA-3′ (SEQ ID NO: 980)5′-CUAUUGUUUUUAGAAAAAAUAAAat-3′ (SEQ ID NO: 327)3′-AAGAUAACAAAAAUCUUUUUUAUUUUA-5′ (SEQ ID NO: 654) MYC-2333 Target:5′-TTCTATTGTTTTTAGAAAAAATAAAAT-3′ (SEQ ID NO: 981)

TABLE 3 Selected Human Anti-MYC DsiRNAs, Unmodified Duplexes(Asymmetrics) 5′-CGAGAAGGGCAGGGCUUCUCAGAGG-3′ (SEQ ID NO: 982)3′-GAGCUCUUCCCGUCCCGAAGAGUCUCC-5′ (SEQ ID NO: 328) MYC-94 Target:5′-CTCGAGAAGGGCAGGGCTTCTCAGAGG-3′ (SEQ ID NO: 655)5′-GCUUUAUCUAACUCGCUGUAGUAAU-3′ (SEQ ID NO: 983)3′-CCCGAAAUAGAUUGAGCGACAUCAUUA-5′ (SEQ ID NO: 329) MYC-178 Target:5′-GGGCTTTATCTAACTCGCTGTAGTAAT-3′ (SEQ ID NO: 656)5′-CCCUUGCCGCAUCCACGAAACUUUG-3′ (SEQ ID NO: 984)3′-UUGGGAACGGCGUAGGUGCUUUGAAAC-5′ (SEQ ID NO: 330) MYC-365 Target:5′-AACCCTTGCCGCATCCACGAAACTTTG-3′ (SEQ ID NO: 657)5′-GCCGCAUCCACGAAACUUUGCCCAU-3′ (SEQ ID NO: 985)3′-AACGGCGUAGGUGCUUUGAAACGGGUA-5′ (SEQ ID NO: 331) MYC-370 Target:5′-TTGCCGCATCCACGAAACTTTGCCCAT-3′ (SEQ ID NO: 658)5′-UCCACGAAACUUUGCCCAUAGCAGC-3′ (SEQ ID NO: 986)3′-GUAGGUGCUUUGAAACGGGUAUCGUCG-5′ (SEQ ID NO: 332) MYC-376 Target:5′-CATCCACGAAACTTTGCCCATAGCAGC-3′ (SEQ ID NO: 659)5′-GCGGGCACUUUGCACUGGAACUUAC-3′ (SEQ ID NO: 987)3′-CCCGCCCGUGAAACGUGACCUUGAAUG-5′ (SEQ ID NO: 333) MYC-403 Target:5′-GGGCGGGCACTTTGCACTGGAACTTAC-3′ (SEQ ID NO: 660)5′-ACUUUGCACUGGAACUUACAACACC-3′ (SEQ ID NO: 988)3′-CGUGAAACGUGACCUUGAAUGUUGUGG-5′ (SEQ ID NO: 334) MYC-409 Target:5′-GCACTTTGCACTGGAACTTACAACACC-3′ (SEQ ID NO: 661)5′-CUGGAACUUACAACACCCGAGCAAG-3′ (SEQ ID NO: 989)3′-GUGACCUUGAAUGUUGUGGGCUCGUUC-5′ (SEQ ID NO: 335) MYC-417 Target:5′-CACTGGAACTTACAACACCCGAGCAAG-3′ (SEQ ID NO: 662)5′-GCAGCUGCUUAGACGCUGGAUUUUU-3′ (SEQ ID NO: 990)3′-AACGUCGACGAAUCUGCGACCUAAAAA-5′ (SEQ ID NO: 336) MYC-535 Target:5′-TTGCAGCTGCTTAGACGCTGGATTTTT-3′ (SEQ ID NO: 663)5′-GCUUAGACGCUGGAUUUUUUUCGGG-3′ (SEQ ID NO: 991)3′-GACGAAUCUGCGACCUAAAAAAAGCCC-5′ (SEQ ID NO: 337) MYC-541 Target:5′-CTGCTTAGACGCTGGATTTTTTTCGGG-3′ (SEQ ID NO: 664)5′-CGCUGGAUUUUUUUCGGGUAGUGGA-3′ (SEQ ID NO: 992)3′-CUGCGACCUAAAAAAAGCCCAUCACCU-5′ (SEQ ID NO: 338) MYC-548 Target:5′-GACGCTGGATTTTTTTCGGGTAGTGGA-3′ (SEQ ID NO: 665)5′-GAUUUUUUUCGGGUAGUGGAAAACC-3′ (SEQ ID NO: 993)3′-ACCUAAAAAAAGCCCAUCACCUUUUGG-5′ (SEQ ID NO: 339) MYC-553 Target:5′-TGGATTTTTTTCGGGTAGTGGAAAACC-3′ (SEQ ID NO: 666)5′-CGGGUAGUGGAAAACCAGCAGCCUC-3′ (SEQ ID NO: 994)3′-AAGCCCAUCACCUUUUGGUCGUCGGAG-5′ (SEQ ID NO: 340) MYC-562 Target:5′-TTCGGGTAGTGGAAAACCAGCAGCCTC-3′ (SEQ ID NO: 667)5′-CUCAACGUUAGCUUCACCAACAGGA-3′ (SEQ ID NO: 995)3′-GGGAGUUGCAAUCGAAGUGGUUGUCCU-5′ (SEQ ID NO: 341) MYC-601 Target:5′-CCCTCAACGTTAGCTTCACCAACAGGA-3′ (SEQ ID NO: 668)5′-GUUAGCUUCACCAACAGGAACUAUG-3′ (SEQ ID NO: 996)3′-UGCAAUCGAAGUGGUUGUCCUUGAUAC-5′ (SEQ ID NO: 342) MYC-607 Target:5′-ACGTTAGCTTCACCAACAGGAACTATG-3′ (SEQ ID NO: 669)5′-GACUCGGUGCAGCCGUAUUUCUACU-3′ (SEQ ID NO: 997)3′-UGCUGAGCCACGUCGGCAUAAAGAUGA-5′ (SEQ ID NO: 343) MYC-643 Target:5′-ACGACTCGGTGCAGCCGTATTTCTACT-3′ (SEQ ID NO: 670)5′-GCAGCCGUAUUUCUACUGCGACGAG-3′ (SEQ ID NO: 998)3′-CACGUCGGCAUAAAGAUGACGCUGCUC-5′ (SEQ ID NO: 344) MYC-651 Target:5′-GTGCAGCCGTATTTCTACTGCGACGAG-3′ (SEQ ID NO: 671)5′-GAGGAGAACUUCUACCAGCAGCAGC-3′ (SEQ ID NO: 999)3′-UCCUCCUCUUGAAGAUGGUCGUCGUCG-5′ (SEQ ID NO: 345) MYC-676 Target:5′-AGGAGGAGAACTTCTACCAGCAGCAGC-3′ (SEQ ID NO: 672)5′-GCGAGGAUAUCUGGAAGAAAUUCGA-3′ (SEQ ID NO: 1000)3′-GUCGCUCCUAUAGACCUUCUUUAAGCU-5′ (SEQ ID NO: 346) MYC-731 Target:5′-CAGCGAGGATATCTGGAAGAAATTCGA-3′ (SEQ ID NO: 673)5′-CGUUGCGGUCACACCCUUCUCCCUU-3′ (SEQ ID NO: 1001)3′-AUGCAACGCCAGUGUGGGAAGAGGGAA-5′ (SEQ ID NO: 347) MYC-816 Target:5′-TACGTTGCGGTCACACCCTTCTCCCTT-3′ (SEQ ID NO: 674)5′-ACAUGGUGAACCAGAGUUUCAUCUG-3′ (SEQ ID NO: 1002)3′-UCUGUACCACUUGGUCUCAAAGUAGAC-5′ (SEQ ID NO: 348) MYC-920 Target:5′-AGACATGGTGAACCAGAGTTTCATCTG-3′ (SEQ ID NO: 675)5′-CCGGACGACGAGACCUUCAUCAAAA-3′ (SEQ ID NO: 1003)3′-UGGGCCUGCUGCUCUGGAAGUAGUUUU-5′ (SEQ ID NO: 349) MYC-949 Target:5′-ACCCGGACGACGAGACCTTCATCAAAA-3′ (SEQ ID NO: 676)5′-GAGACCUUCAUCAAAAACAUCAUCA-3′ (SEQ ID NO: 1004)3′-UGCUCUGGAAGUAGUUUUUGUAGUAGU-5′ (SEQ ID NO: 350) MYC-958 Target:5′-ACGAGACCTTCATCAAAAACATCATCA-3′ (SEQ ID NO: 677)5′-AAAAACAUCAUCAUCCAGGACUGUA-3′ (SEQ ID NO: 1005)3′-AGUUUUUGUAGUAGUAGGUCCUGACAU-5′ (SEQ ID NO: 351) MYC-970 Target:5′-TCAAAAACATCATCATCCAGGACTGTA-3′ (SEQ ID NO: 678)5′-GGACUGUAUGUGGAGCGGCUUCUCG-3′ (SEQ ID NO: 1006)3′-GUCCUGACAUACACCUCGCCGAAGAGC-5′ (SEQ ID NO: 352) MYC-987 Target:5′-CAGGACTGTATGTGGAGCGGCTTCTCG-3′ (SEQ ID NO: 679)5′-CUGCUCCACCUCCAGCUUGUACCUG-3′ (SEQ ID NO: 1007)3′-CAGACGAGGUGGAGGUCGAACAUGGAC-5′ (SEQ ID NO: 353) MYC-1104 Target:5′-GTCTGCTCCACCTCCAGCTTGTACCTG-3′ (SEQ ID NO: 680)5′-ACCUCCAGCUUGUACCUGCAGGAUC-3′ (SEQ ID NO: 1008)3′-GGUGGAGGUCGAACAUGGACGUCCUAG-5′ (SEQ ID NO: 354) MYC-1111 Target:5′-CCACCTCCAGCTTGTACCTGCAGGATC-3′ (SEQ ID NO: 681)5′-CAGCUUGUACCUGCAGGAUCUGAGC-3′ (SEQ ID NO: 1009)3′-AGGUCGAACAUGGACGUCCUAGACUCG-5′ (SEQ ID NO: 355) MYC-1116 Target:5′-TCCAGCTTGTACCTGCAGGATCTGAGC-3′ (SEQ ID NO: 682)5′-AAGUCCUGCGCCUCGCAAGACUCCA-3′ (SEQ ID NO: 1010)3′-GGUUCAGGACGCGGAGCGUUCUGAGGU-5′ (SEQ ID NO: 356) MYC-1210 Target:5′-CCAAGTCCTGCGCCTCGCAAGACTCCA-3′ (SEQ ID NO: 683)5′-GCAGCGACUCUGAGGAGGAACAAGA-3′ (SEQ ID NO: 1011)3′-GUCGUCGCUGAGACUCCUCCUUGUUCU-5′ (SEQ ID NO: 357) MYC-1340 Target:5′-CAGCAGCGACTCTGAGGAGGAACAAGA-3′ (SEQ ID NO: 684)5′-ACUCUGAGGAGGAACAAGAAGAUGA-3′ (SEQ ID NO: 1012)3′-GCUGAGACUCCUCCUUGUUCUUCUACU-5′ (SEQ ID NO: 358) MYC-1346 Target:5′-CGACTCTGAGGAGGAACAAGAAGATGA-3′ (SEQ ID NO: 685)5′-GAGGAGGAACAAGAAGAUGAGGAAG-3′ (SEQ ID NO: 1013)3′-GACUCCUCCUUGUUCUUCUACUCCUUC-5′ (SEQ ID NO: 359) MYC-1351 Target:5′-CTGAGGAGGAACAAGAAGATGAGGAAG-3′ (SEQ ID NO: 686)5′-AACAAGAAGAUGAGGAAGAAAUCGA-3′ (SEQ ID NO: 1014)3′-CCUUGUUCUUCUACUCCUUCUUUAGCU-5′ (SEQ ID NO: 360) MYC-1358 Target:5′-GGAACAAGAAGATGAGGAAGAAATCGA-3′ (SEQ ID NO: 687)5′-AAGAUGAGGAAGAAAUCGAUGUUGU-3′ (SEQ ID NO: 1015)3′-UCUUCUACUCCUUCUUUAGCUACAACA-5′ (SEQ ID NO: 361) MYC-1364 Target:5′-AGAAGATGAGGAAGAAATCGATGTTGT-3′ (SEQ ID NO: 688)5′-AGGAAGAAAUCGAUGUUGUUUCUGU-3′ (SEQ ID NO: 1016)3′-ACUCCUUCUUUAGCUACAACAAAGACA-5′ (SEQ ID NO: 362) MYC-1370 Target:5′-TGAGGAAGAAATCGATGTTGTTTCTGT-3′ (SEQ ID NO: 689)5′-AAAUCGAUGUUGUUUCUGUGGAAAA-3′ (SEQ ID NO: 1017)3′-UCUUUAGCUACAACAAAGACACCUUUU-5′ (SEQ ID NO: 363) MYC-1376 Target:5′-AGAAATCGATGTTGTTTCTGTGGAAAA-3′ (SEQ ID NO: 690)5′-AUGUUGUUUCUGUGGAAAAGAGGCA-3′ (SEQ ID NO: 1018)3′-GCUACAACAAAGACACCUUUUCUCCGU-5′ (SEQ ID NO: 364) MYC-1382 Target:5′-CGATGTTGTTTCTGTGGAAAAGAGGCA-3′ (SEQ ID NO: 691)5′-GAGGCAGGCUCCUGGCAAAAGGUCA-3′ (SEQ ID NO: 1019)3′-UUCUCCGUCCGAGGACCGUUUUCCAGU-5′ (SEQ ID NO: 365) MYC-1401 Target:5′-AAGAGGCAGGCTCCTGGCAAAAGGTCA-3′ (SEQ ID NO: 692)5′-AGGCUCCUGGCAAAAGGUCAGAGUC-3′ (SEQ ID NO: 1020)3′-CGUCCGAGGACCGUUUUCCAGUCUCAG-5′ (SEQ ID NO: 366) MYC-1406 Target:5′-GCAGGCTCCTGGCAAAAGGTCAGAGTC-3′ (SEQ ID NO: 693)5′-CCUGGCAAAAGGUCAGAGUCUGGAU-3′ (SEQ ID NO: 1021)3′-GAGGACCGUUUUCCAGUCUCAGACCUA-5′ (SEQ ID NO: 367) MYC-1411 Target:5′-CTCCTGGCAAAAGGTCAGAGTCTGGAT-3′ (SEQ ID NO: 694)5′-CAAAAGGUCAGAGUCUGGAUCACCU-3′ (SEQ ID NO: 1022)3′-CCGUUUUCCAGUCUCAGACCUAGUGGA-5′ (SEQ ID NO: 368) MYC-1416 Target:5′-GGCAAAAGGTCAGAGTCTGGATCACCT-3′ (SEQ ID NO: 695)5′-GGUCAGAGUCUGGAUCACCUUCUGC-3′ (SEQ ID NO: 1023)3′-UUCCAGUCUCAGACCUAGUGGAAGACG-5′ (SEQ ID NO: 369) MYC-1421 Target:5′-AAGGTCAGAGTCTGGATCACCTTCTGC-3′ (SEQ ID NO: 696)5′-GCAAACCUCCUCACAGCCCACUGGU-3′ (SEQ ID NO: 1024)3′-GUCGUUUGGAGGAGUGUCGGGUGACCA-5′ (SEQ ID NO: 370) MYC-1457 Target:5′-CAGCAAACCTCCTCACAGCCCACTGGT-3′ (SEQ ID NO: 697)5′-CCUCACAGCCCACUGGUCCUCAAGA-3′ (SEQ ID NO: 1025)3′-GAGGAGUGUCGGGUGACCAGGAGUUCU-5′ (SEQ ID NO: 371) MYC-1465 Target:5′-CTCCTCACAGCCCACTGGTCCTCAAGA-3′ (SEQ ID NO: 698)5′-CCCUCCACUCGGAAGGACUAUCCUG-3′ (SEQ ID NO: 1026)3′-GAGGGAGGUGAGCCUUCCUGAUAGGAC-5′ (SEQ ID NO: 372) MYC-1531 Target:5′-CTCCCTCCACTCGGAAGGACTATCCTG-3′ (SEQ ID NO: 699)5′-CUCGGAAGGACUAUCCUGCUGCCAA-3′ (SEQ ID NO: 1027)3′-GUGAGCCUUCCUGAUAGGACGACGGUU-5′ (SEQ ID NO: 373) MYC-1538 Target:5′-CACTCGGAAGGACTATCCTGCTGCCAA-3′ (SEQ ID NO: 700)5′-AUCCUGCUGCCAAGAGGGUCAAGUU-3′ (SEQ ID NO: 1028)3′-GAUAGGACGACGGUUCUCCCAGUUCAA-5′ (SEQ ID NO: 374) MYC-1550 Target:5′-CTATCCTGCTGCCAAGAGGGTCAAGTT-3′ (SEQ ID NO: 701)5′-GCUGCCAAGAGGGUCAAGUUGGACA-3′ (SEQ ID NO: 1029)3′-GACGACGGUUCUCCCAGUUCAACCUGU-5′ (SEQ ID NO: 375) MYC-1555 Target:5′-CTGCTGCCAAGAGGGTCAAGTTGGACA-3′ (SEQ ID NO: 702)5′-CAAGAGGGUCAAGUUGGACAGUGUC-3′ (SEQ ID NO: 1030)3′-CGGUUCUCCCAGUUCAACCUGUCACAG-5′ (SEQ ID NO: 376) MYC-1560 Target:5′-GCCAAGAGGGTCAAGTTGGACAGTGTC-3′ (SEQ ID NO: 703)5′-GGGUCAAGUUGGACAGUGUCAGAGU-3′ (SEQ ID NO: 1031)3′-CUCCCAGUUCAACCUGUCACAGUCUCA-5′ (SEQ ID NO: 377) MYC-1565 Target:5′-GAGGGTCAAGTTGGACAGTGTCAGAGT-3′ (SEQ ID NO: 704)5′-AAGUUGGACAGUGUCAGAGUCCUGA-3′ (SEQ ID NO: 1032)3′-AGUUCAACCUGUCACAGUCUCAGGACU-5′ (SEQ ID NO: 378) MYC-1570 Target:5′-TCAAGTTGGACAGTGTCAGAGTCCTGA-3′ (SEQ ID NO: 705)5′-GGACAGUGUCAGAGUCCUGAGACAG-3′ (SEQ ID NO: 1033)3′-AACCUGUCACAGUCUCAGGACUCUGUC-5′ (SEQ ID NO: 379) MYC-1575 Target:5′-TTGGACAGTGTCAGAGTCCTGAGACAG-3′ (SEQ ID NO: 706)5′-CAGAGUCCUGAGACAGAUCAGCAAC-3′ (SEQ ID NO: 1034)3′-CAGUCUCAGGACUCUGUCUAGUCGUUG-5′ (SEQ ID NO: 380) MYC-1584 Target:5′-GTCAGAGTCCTGAGACAGATCAGCAAC-3′ (SEQ ID NO: 707)5′-GAGACAGAUCAGCAACAACCGAAAA-3′ (SEQ ID NO: 1035)3′-GACUCUGUCUAGUCGUUGUUGGCUUUU-5′ (SEQ ID NO: 381) MYC-1593 Target:5′-CTGAGACAGATCAGCAACAACCGAAAA-3′ (SEQ ID NO: 708)5′-GAUCAGCAACAACCGAAAAUGCACC-3′ (SEQ ID NO: 1036)3′-GUCUAGUCGUUGUUGGCUUUUACGUGG-5′ (SEQ ID NO: 382) MYC-1599 Target:5′-CAGATCAGCAACAACCGAAAATGCACC-3′ (SEQ ID NO: 709)5′-CCUCGGACACCGAGGAGAAUGUCAA-3′ (SEQ ID NO: 1037)3′-CAGGAGCCUGUGGCUCCUCUUACAGUU-5′ (SEQ ID NO: 383) MYC-1634 Target:5′-GTCCTCGGACACCGAGGAGAATGTCAA-3′ (SEQ ID NO: 710)5′-GACACCGAGGAGAAUGUCAAGAGGC-3′ (SEQ ID NO: 1038)3′-GCCUGUGGCUCCUCUUACAGUUCUCCG-5′ (SEQ ID NO: 384) MYC-1639 Target:5′-CGGACACCGAGGAGAATGTCAAGAGGC-3′ (SEQ ID NO: 711)5′-CAGAGGAGGAACGAGCUAAAACGGA-3′ (SEQ ID NO: 1039)3′-CGGUCUCCUCCUUGCUCGAUUUUGCCU-5′ (SEQ ID NO: 385) MYC-1687 Target:5′-GCCAGAGGAGGAACGAGCTAAAACGGA-3′ (SEQ ID NO: 712)5′-AGGAACGAGCUAAAACGGAGCUUUU-3′ (SEQ ID NO: 1040)3′-CCUCCUUGCUCGAUUUUGCCUCGAAAA-5′ (SEQ ID NO: 386) MYC-1693 Target:5′-GGAGGAACGAGCTAAAACGGAGCTTTT-3′ (SEQ ID NO: 713)5′-CGAGCUAAAACGGAGCUUUUUUGCC-3′ (SEQ ID NO: 1041)3′-UUGCUCGAUUUUGCCUCGAAAAAACGG-5′ (SEQ ID NO: 387) MYC-1698 Target:5′-AACGAGCTAAAACGGAGCTTTTTTGCC-3′ (SEQ ID NO: 714)5′-AAAACGGAGCUUUUUUGCCCUGCGU-3′ (SEQ ID NO: 1042)3′-GAUUUUGCCUCGAAAAAACGGGACGCA-5′ (SEQ ID NO: 388) MYC-1704 Target:5′-CTAAAACGGAGCTTTTTTGCCCTGCGT-3′ (SEQ ID NO: 715)5′-GGAGCUUUUUUGCCCUGCGUGACCA-3′ (SEQ ID NO: 1043)3′-UGCCUCGAAAAAACGGGACGCACUGGU-5′ (SEQ ID NO: 389) MYC-1709 Target:5′-ACGGAGCTTTTTTGCCCTGCGTGACCA-3′ (SEQ ID NO: 716)5′-GACCAGAUCCCGGAGUUGGAAAACA-3′ (SEQ ID NO: 1044)3′-CACUGGUCUAGGGCCUCAACCUUUUGU-5′ (SEQ ID NO: 390) MYC-1729 Target:5′-GTGACCAGATCCCGGAGTTGGAAAACA-3′ (SEQ ID NO: 717)5′-GAUCCCGGAGUUGGAAAACAAUGAA-3′ (SEQ ID NO: 1045)3′-GUCUAGGGCCUCAACCUUUUGUUACUU-5′ (SEQ ID NO: 391) MYC-1734 Target:5′-CAGATCCCGGAGTTGGAAAACAATGAA-3′ (SEQ ID NO: 718)5′-CGGAGUUGGAAAACAAUGAAAAGGC-3′ (SEQ ID NO: 1046)3′-GGGCCUCAACCUUUUGUUACUUUUCCG-5′ (SEQ ID NO: 392) MYC-1739 Target:5′-CCCGGAGTTGGAAAACAATGAAAAGGC-3′ (SEQ ID NO: 719)5′-AGGUAGUUAUCCUUAAAAAAGCCAC-3′ (SEQ ID NO: 1047)3′-GUUCCAUCAAUAGGAAUUUUUUCGGUG-5′ (SEQ ID NO: 393) MYC-1769 Target:5′-CAAGGTAGTTATCCTTAAAAAAGCCAC-3′ (SEQ ID NO: 720)5′-GUUAUCCUUAAAAAAGCCACAGCAU-3′ (SEQ ID NO: 1048)3′-AUCAAUAGGAAUUUUUUCGGUGUCGUA-5′ (SEQ ID NO: 394) MYC-1774 Target:5′-TAGTTATCCTTAAAAAAGCCACAGCAT-3′ (SEQ ID NO: 721)5′-CCUUAAAAAAGCCACAGCAUACAUC-3′ (SEQ ID NO: 1049)3′-UAGGAAUUUUUUCGGUGUCGUAUGUAG-5′ (SEQ ID NO: 395) MYC-1779 Target:5′-ATCCTTAAAAAAGCCACAGCATACATC-3′ (SEQ ID NO: 722)5′-AAAAAGCCACAGCAUACAUCCUGUC-3′ (SEQ ID NO: 1050)3′-AUUUUUUCGGUGUCGUAUGUAGGACAG-5′ (SEQ ID NO: 396) MYC-1784 Target:5′-TAAAAAAGCCACAGCATACATCCTGTC-3′ (SEQ ID NO: 723)5′-GCCACAGCAUACAUCCUGUCCGUCC-3′ (SEQ ID NO: 1051)3′-UUCGGUGUCGUAUGUAGGACAGGCAGG-5′ (SEQ ID NO: 397) MYC-1789 Target:5′-AAGCCACAGCATACATCCTGTCCGTCC-3′ (SEQ ID NO: 724)5′-GCAUACAUCCUGUCCGUCCAAGCAG-3′ (SEQ ID NO: 1052)3′-GUCGUAUGUAGGACAGGCAGGUUCGUC-5′ (SEQ ID NO: 398) MYC-1795 Target:5′-CAGCATACATCCTGTCCGTCCAAGCAG-3′ (SEQ ID NO: 725)5′-CCUGUCCGUCCAAGCAGAGGAGCAA-3′ (SEQ ID NO: 1053)3′-UAGGACAGGCAGGUUCGUCUCCUCGUU-5′ (SEQ ID NO: 399) MYC-1803 Target:5′-ATCCTGTCCGTCCAAGCAGAGGAGCAA-3′ (SEQ ID NO: 726)5′-CCGUCCAAGCAGAGGAGCAAAAGCU-3′ (SEQ ID NO: 1054)3′-CAGGCAGGUUCGUCUCCUCGUUUUCGA-5′ (SEQ ID NO: 400) MYC-1808 Target:5′-GTCCGTCCAAGCAGAGGAGCAAAAGCT-3′ (SEQ ID NO: 727)5′-GCAGAGGAGCAAAAGCUCAUUUCUG-3′ (SEQ ID NO: 1055)3′-UUCGUCUCCUCGUUUUCGAGUAAAGAC-5′ (SEQ ID NO: 401) MYC-1816 Target:5′-AAGCAGAGGAGCAAAAGCTCATTTCTG-3′ (SEQ ID NO: 728)5′-AGCAAAAGCUCAUUUCUGAAGAGGA-3′ (SEQ ID NO: 1056)3′-CCUCGUUUUCGAGUAAAGACUUCUCCU-5′ (SEQ ID NO: 402) MYC-1823 Target:5′-GGAGCAAAAGCTCATTTCTGAAGAGGA-3′ (SEQ ID NO: 729)5′-AAGCUCAUUUCUGAAGAGGACUUGU-3′ (SEQ ID NO: 1057)3′-UUUUCGAGUAAAGACUUCUCCUGAACA-5′ (SEQ ID NO: 403) MYC-1828 Target:5′-AAAAGCTCATTTCTGAAGAGGACTTGT-3′ (SEQ ID NO: 730)5′-AUUUCUGAAGAGGACUUGUUGCGGA-3′ (SEQ ID NO: 1058)3′-AGUAAAGACUUCUCCUGAACAACGCCU-5′ (SEQ ID NO: 404) MYC-1834 Target:5′-TCATTTCTGAAGAGGACTTGTTGCGGA-3′ (SEQ ID NO: 731)5′-GAAGAGGACUUGUUGCGGAAACGAC-3′ (SEQ ID NO: 1059)3′-GACUUCUCCUGAACAACGCCUUUGCUG-5′ (SEQ ID NO: 405) MYC-1840 Target:5′-CTGAAGAGGACTTGTTGCGGAAACGAC-3′ (SEQ ID NO: 732)5′-GGACUUGUUGCGGAAACGACGAGAA-3′ (SEQ ID NO: 1060)3′-CUCCUGAACAACGCCUUUGCUGCUCUU-5′ (SEQ ID NO: 406) MYC-1845 Target:5′-GAGGACTTGTTGCGGAAACGACGAGAA-3′ (SEQ ID NO: 733)5′-UGUUGCGGAAACGACGAGAACAGUU-3′ (SEQ ID NO: 1061)3′-GAACAACGCCUUUGCUGCUCUUGUCAA-5′ (SEQ ID NO: 407) MYC-1850 Target:5′-CTTGTTGCGGAAACGACGAGAACAGTT-3′ (SEQ ID NO: 734)5′-CGGAAACGACGAGAACAGUUGAAAC-3′ (SEQ ID NO: 1062)3′-ACGCCUUUGCUGCUCUUGUCAACUUUG-5′ (SEQ ID NO: 408) MYC-1855 Target:5′-TGCGGAAACGACGAGAACAGTTGAAAC-3′ (SEQ ID NO: 735)5′-AAACUUGAACAGCUACGGAACUCUU-3′ (SEQ ID NO: 1063)3′-UGUUUGAACUUGUCGAUGCCUUGAGAA-5′ (SEQ ID NO: 409) MYC-1882 Target:5′-ACAAACTTGAACAGCTACGGAACTCTT-3′ (SEQ ID NO: 736)5′-GAACAGCUACGGAACUCUUGUGCGU-3′ (SEQ ID NO: 1064)3′-AACUUGUCGAUGCCUUGAGAACACGCA-5′ (SEQ ID NO: 410) MYC-1888 Target:5′-TTGAACAGCTACGGAACTCTTGTGCGT-3′ (SEQ ID NO: 737)5′-GCUACGGAACUCUUGUGCGUAAGGA-3′ (SEQ ID NO: 1065)3′-GUCGAUGCCUUGAGAACACGCAUUCCU-5′ (SEQ ID NO: 411) MYC-1893 Target:5′-CAGCTACGGAACTCTTGTGCGTAAGGA-3′ (SEQ ID NO: 738)5′-AACUCUUGUGCGUAAGGAAAAGUAA-3′ (SEQ ID NO: 1066)3′-CCUUGAGAACACGCAUUCCUUUUCAUU-5′ (SEQ ID NO: 412) MYC-1900 Target:5′-GGAACTCTTGTGCGTAAGGAAAAGTAA-3′ (SEQ ID NO: 739)5′-UGUGCGUAAGGAAAAGUAAGGAAAA-3′ (SEQ ID NO: 1067)3′-GAACACGCAUUCCUUUUCAUUCCUUUU-5′ (SEQ ID NO: 413) MYC-1906 Target:5′-CTTGTGCGTAAGGAAAAGTAAGGAAAA-3′ (SEQ ID NO: 740)5′-GUAAGGAAAAGUAAGGAAAACGAUU-3′ (SEQ ID NO: 1068)3′-CGCAUUCCUUUUCAUUCCUUUUGCUAA-5′ (SEQ ID NO: 414) MYC-1911 Target:5′-GCGTAAGGAAAAGTAAGGAAAACGATT-3′ (SEQ ID NO: 741)5′-GUAAGGAAAACGAUUCCUUCUAACA-3′ (SEQ ID NO: 1069)3′-UUCAUUCCUUUUGCUAAGGAAGAUUGU-5′ (SEQ ID NO: 415) MYC-1921 Target:5′-AAGTAAGGAAAACGATTCCTTCTAACA-3′ (SEQ ID NO: 742)5′-GAAAACGAUUCCUUCUAACAGAAAU-3′ (SEQ ID NO: 1070)3′-UCCUUUUGCUAAGGAAGAUUGUCUUUA-5′ (SEQ ID NO: 416) MYC-1926 Target:5′-AGGAAAACGATTCCTTCTAACAGAAAT-3′ (SEQ ID NO: 743)5′-CGAUUCCUUCUAACAGAAAUGUCCU-3′ (SEQ ID NO: 1071)3′-UUGCUAAGGAAGAUUGUCUUUACAGGA-5′ (SEQ ID NO: 417) MYC-1931 Target:5′-AACGATTCCTTCTAACAGAAATGTCCT-3′ (SEQ ID NO: 744)5′-CUUCUAACAGAAAUGUCCUGAGCAA-3′ (SEQ ID NO: 1072)3′-AGGAAGAUUGUCUUUACAGGACUCGUU-5′ (SEQ ID NO: 418) MYC-1937 Target:5′-TCCTTCTAACAGAAATGTCCTGAGCAA-3′ (SEQ ID NO: 745)5′-CAGAAAUGUCCUGAGCAAUCACCUA-3′ (SEQ ID NO: 1073)3′-UUGUCUUUACAGGACUCGUUAGUGGAU-5′ (SEQ ID NO: 419) MYC-1944 Target:5′-AACAGAAATGTCCTGAGCAATCACCTA-3′ (SEQ ID NO: 746)5′-CCUGAGCAAUCACCUAUGAACUUGU-3′ (SEQ ID NO: 1074)3′-CAGGACUCGUUAGUGGAUACUUGAACA-5′ (SEQ ID NO: 420) MYC-1953 Target:5′-GTCCTGAGCAATCACCTATGAACTTGT-3′ (SEQ ID NO: 747)5′-CAAUCACCUAUGAACUUGUUUCAAA-3′ (SEQ ID NO: 1075)3′-UCGUUAGUGGAUACUUGAACAAAGUUU-5′ (SEQ ID NO: 421) MYC-1959 Target:5′-AGCAATCACCTATGAACTTGTTTCAAA-3′ (SEQ ID NO: 748)5′-CCUAUGAACUUGUUUCAAAUGCAUG-3′ (SEQ ID NO: 1076)3′-GUGGAUACUUGAACAAAGUUUACGUAC-5′ (SEQ ID NO: 422) MYC-1965 Target:5′-CACCTATGAACTTGTTTCAAATGCATG-3′ (SEQ ID NO: 749)5′-GAACUUGUUUCAAAUGCAUGAUCAA-3′ (SEQ ID NO: 1077)3′-UACUUGAACAAAGUUUACGUACUAGUU-5′ (SEQ ID NO: 423) MYC-1970 Target:5′-ATGAACTTGTTTCAAATGCATGATCAA-3′ (SEQ ID NO: 750)5′-GUUUCAAAUGCAUGAUCAAAUGCAA-3′ (SEQ ID NO: 1078)3′-AACAAAGUUUACGUACUAGUUUACGUU-5′ (SEQ ID NO: 424) MYC-1976 Target:5′-TTGTTTCAAATGCATGATCAAATGCAA-3′ (SEQ ID NO: 751)5′-AAAUGCAUGAUCAAAUGCAACCUCA-3′ (SEQ ID NO: 1079)3′-AGUUUACGUACUAGUUUACGUUGGAGU-5′ (SEQ ID NO: 425) MYC-1981 Target:5′-TCAAATGCATGATCAAATGCAACCTCA-3′ (SEQ ID NO: 752)5′-GAUCAAAUGCAACCUCACAACCUUG-3′ (SEQ ID NO: 1080)3′-UACUAGUUUACGUUGGAGUGUUGGAAC-5′ (SEQ ID NO: 426) MYC-1989 Target:5′-ATGATCAAATGCAACCTCACAACCTTG-3′ (SEQ ID NO: 753)5′-AAUGCAACCUCACAACCUUGGCUGA-3′ (SEQ ID NO: 1081)3′-GUUUACGUUGGAGUGUUGGAACCGACU-5′ (SEQ ID NO: 427) MYC-1994 Target:5′-CAAATGCAACCTCACAACCTTGGCTGA-3′ (SEQ ID NO: 754)5′-CCUCACAACCUUGGCUGAGUCUUGA-3′ (SEQ ID NO: 1082)3′-UUGGAGUGUUGGAACCGACUCAGAACU-5′ (SEQ ID NO: 428) MYC-2001 Target:5′-AACCTCACAACCTTGGCTGAGTCTTGA-3′ (SEQ ID NO: 755)5′-CAACCUUGGCUGAGUCUUGAGACUG-3′ (SEQ ID NO: 1083)3′-GUGUUGGAACCGACUCAGAACUCUGAC-5′ (SEQ ID NO: 429) MYC-2006 Target:5′-CACAACCTTGGCTGAGTCTTGAGACTG-3′ (SEQ ID NO: 756)5′-GGCUGAGUCUUGAGACUGAAAGAUU-3′ (SEQ ID NO: 1084)3′-AACCGACUCAGAACUCUGACUUUCUAA-5′ (SEQ ID NO: 430) MYC-2013 Target:5′-TTGGCTGAGTCTTGAGACTGAAAGATT-3′ (SEQ ID NO: 757)5′-GUCUUGAGACUGAAAGAUUUAGCCA-3′ (SEQ ID NO: 1085)3′-CUCAGAACUCUGACUUUCUAAAUCGGU-5′ (SEQ ID NO: 431) MYC-2019 Target:5′-GAGTCTTGAGACTGAAAGATTTAGCCA-3′ (SEQ ID NO: 758)5′-GACUGAAAGAUUUAGCCAUAAUGUA-3′ (SEQ ID NO: 1086)3′-CUCUGACUUUCUAAAUCGGUAUUACAU-5′ (SEQ ID NO: 432) MYC-2026 Target:5′-GAGACTGAAAGATTTAGCCATAATGTA-3′ (SEQ ID NO: 759)5′-AAAGAUUUAGCCAUAAUGUAAACUG-3′ (SEQ ID NO: 1087)3′-ACUUUCUAAAUCGGUAUUACAUUUGAC-5′ (SEQ ID NO: 433) MYC-2031 Target:5′-TGAAAGATTTAGCCATAATGTAAACTG-3′ (SEQ ID NO: 760)5′-GCCAUAAUGUAAACUGCCUCAAAUU-3′ (SEQ ID NO: 1088)3′-AUCGGUAUUACAUUUGACGGAGUUUAA-5′ (SEQ ID NO: 434) MYC-2040 Target:5′-TAGCCATAATGTAAACTGCCTCAAATT-3′ (SEQ ID NO: 761)5′-GUAAACUGCCUCAAAUUGGACUUUG-3′ (SEQ ID NO: 1089)3′-UACAUUUGACGGAGUUUAACCUGAAAC-5′ (SEQ ID NO: 435) MYC-2048 Target:5′-ATGTAAACTGCCTCAAATTGGACTTTG-3′ (SEQ ID NO: 762)5′-UGCCUCAAAUUGGACUUUGGGCAUA-3′ (SEQ ID NO: 1090)3′-UGACGGAGUUUAACCUGAAACCCGUAU-5′ (SEQ ID NO: 436) MYC-2054 Target:5′-ACTGCCTCAAATTGGACTTTGGGCATA-3′ (SEQ ID NO: 763)5′-CAAAUUGGACUUUGGGCAUAAAAGA-3′ (SEQ ID NO: 1091)3′-GAGUUUAACCUGAAACCCGUAUUUUCU-5′ (SEQ ID NO: 437) MYC-2059 Target:5′-CTCAAATTGGACTTTGGGCATAAAAGA-3′ (SEQ ID NO: 764)5′-GACUUUGGGCAUAAAAGAACUUUUU-3′ (SEQ ID NO: 1092)3′-ACCUGAAACCCGUAUUUUCUUGAAAAA-5′ (SEQ ID NO: 438) MYC-2066 Target:5′-TGGACTTTGGGCATAAAAGAACTTTTT-3′ (SEQ ID NO: 765)5′-GGCAUAAAAGAACUUUUUUAUGCUU-3′ (SEQ ID NO: 1093)3′-ACCCGUAUUUUCUUGAAAAAAUACGAA-5′ (SEQ ID NO: 439) MYC-2073 Target:5′-TGGGCATAAAAGAACTTTTTTATGCTT-3′ (SEQ ID NO: 766)5′-AAAAGAACUUUUUUAUGCUUACCAU-3′ (SEQ ID NO: 1094)3′-UAUUUUCUUGAAAAAAUACGAAUGGUA-5′ (SEQ ID NO: 440) MYC-2078 Target:5′-ATAAAAGAACTTTTTTATGCTTACCAT-3′ (SEQ ID NO: 767)5′-AACUUUUUUAUGCUUACCAUCUUUU-3′ (SEQ ID NO: 1095)3′-UCUUGAAAAAAUACGAAUGGUAGAAAA-5′ (SEQ ID NO: 441) MYC-2083 Target:5′-AGAACTTTTTTATGCTTACCATCTTTT-3′ (SEQ ID NO: 768)5′-UUUAUGCUUACCAUCUUUUUUUUUU-3′ (SEQ ID NO: 1096)3′-AAAAAUACGAAUGGUAGAAAAAAAAAA-5′ (SEQ ID NO: 442) MYC-2089 Target:5′-TTTTTATGCTTACCATCTTTTTTTTTT-3′ (SEQ ID NO: 769)5′-GCUUACCAUCUUUUUUUUUUCUUUA-3′ (SEQ ID NO: 1097)3′-UACGAAUGGUAGAAAAAAAAAAGAAAU-5′ (SEQ ID NO: 443) MYC-2094 Target:5′-ATGCTTACCATCTTTTTTTTTTCTTTA-3′ (SEQ ID NO: 770)5′-CCAUCUUUUUUUUUUCUUUAACAGA-3′ (SEQ ID NO: 1098)3′-AUGGUAGAAAAAAAAAAGAAAUUGUCU-5′ (SEQ ID NO: 444) MYC-2099 Target:5′-TACCATCTTTTTTTTTTCTTTAACAGA-3′ (SEQ ID NO: 771)5′-UUUUUUUUUCUUUAACAGAUUUGUA-3′ (SEQ ID NO: 1099)3′-GAAAAAAAAAAGAAAUUGUCUAAACAU-5′ (SEQ ID NO: 445) MYC-2105 Target:5′-CTTTTTTTTTTCTTTAACAGATTTGTA-3′ (SEQ ID NO: 772)5′-CUUUAACAGAUUUGUAUUUAAGAAU-3′ (SEQ ID NO: 1100)3′-AAGAAAUUGUCUAAACAUAAAUUCUUA-5′ (SEQ ID NO: 446) MYC-2114 Target:5′-TTCTTTAACAGATTTGTATTTAAGAAT-3′ (SEQ ID NO: 773)5′-CAGAUUUGUAUUUAAGAAUUGUUUU-3′ (SEQ ID NO: 1101)3′-UUGUCUAAACAUAAAUUCUUAACAAAA-5′ (SEQ ID NO: 447) MYC-2120 Target:5′-AACAGATTTGTATTTAAGAATTGTTTT-3′ (SEQ ID NO: 774)5′-UAUUUAAGAAUUGUUUUUAAAAAAU-3′ (SEQ ID NO: 1102)3′-ACAUAAAUUCUUAACAAAAAUUUUUUA-5′ (SEQ ID NO: 448) MYC-2128 Target:5′-TGTATTTAAGAATTGTTTTTAAAAAAT-3′ (SEQ ID NO: 775)5′-GAAUUGUUUUUAAAAAAUUUUAAGA-3′ (SEQ ID NO: 1103)3′-UUCUUAACAAAAAUUUUUUAAAAUUCU-5′ (SEQ ID NO: 449) MYC-2135 Target:5′-AAGAATTGTTTTTAAAAAATTTTAAGA-3′ (SEQ ID NO: 776)5′-AAUGUUUCUCUGUAAAUAUUGCCAU-3′ (SEQ ID NO: 1104)3′-UGUUACAAAGAGACAUUUAUAACGGUA-5′ (SEQ ID NO: 450) MYC-2167 Target:5′-ACAATGTTTCTCTGTAAATATTGCCAT-3′ (SEQ ID NO: 777)5′-CUGUAAAUAUUGCCAUUAAAUGUAA-3′ (SEQ ID NO: 1105)3′-GAGACAUUUAUAACGGUAAUUUACAUU-5′ (SEQ ID NO: 451) MYC-2176 Target:5′-CTCTGTAAATATTGCCATTAAATGTAA-3′ (SEQ ID NO: 778)5′-AAUAUUGCCAUUAAAUGUAAAUAAC-3′ (SEQ ID NO: 1106)3′-AUUUAUAACGGUAAUUUACAUUUAUUG-5′ (SEQ ID NO: 452) MYC-2181 Target:5′-TAAATATTGCCATTAAATGTAAATAAC-3′ (SEQ ID NO: 779)5′-CCAUUAAAUGUAAAUAACUUUAAUA-3′ (SEQ ID NO: 1107)3′-ACGGUAAUUUACAUUUAUUGAAAUUAU-5′ (SEQ ID NO: 453) MYC-2188 Target:5′-TGCCATTAAATGTAAATAACTTTAATA-3′ (SEQ ID NO: 780)5′-UUAAUAAAACGUUUAUAGCAGUUAC-3′ (SEQ ID NO: 1108)3′-GAAAUUAUUUUGCAAAUAUCGUCAAUG-5′ (SEQ ID NO: 454) MYC-2207 Target:5′-CTTTAATAAAACGTTTATAGCAGTTAC-3′ (SEQ ID NO: 781)5′-CAGAAUUUCAAUCCUAGUAUAUAGU-3′ (SEQ ID NO: 1109)3′-GUGUCUUAAAGUUAGGAUCAUAUAUCA-5′ (SEQ ID NO: 455) MYC-2233 Target:5′-CACAGAATTTCAATCCTAGTATATAGT-3′ (SEQ ID NO: 782)5′-CUAGUAUUAUAGGUACUAUAAACCC-3′ (SEQ ID NO: 1110)3′-UGGAUCAUAAUAUCCAUGAUAUUUGGG-5′ (SEQ ID NO: 456) MYC-2260 Target:5′-ACCTAGTATTATAGGTACTATAAACCC-3′ (SEQ ID NO: 783)5′-UAUAGGUACUAUAAACCCUAAUUUU-3′ (SEQ ID NO: 1111)3′-UAAUAUCCAUGAUAUUUGGGAUUAAAA-5′ (SEQ ID NO: 457) MYC-2267 Target:5′-ATTATAGGTACTATAAACCCTAATTTT-3′ (SEQ ID NO: 784)5′-ACUAUAAACCCUAAUUUUUUUUAUU-3′ (SEQ ID NO: 1112)3′-CAUGAUAUUUGGGAUUAAAAAAAAUAA-5′ (SEQ ID NO: 458) MYC-2274 Target:5′-GTACTATAAACCCTAATTTTTTTTATT-3′ (SEQ ID NO: 785)5′-CCCUAAUUUUUUUUAUUUAAGUACA-3′ (SEQ ID NO: 1113)3′-UUGGGAUUAAAAAAAAUAAAUUCAUGU-5′ (SEQ ID NO: 459) MYC-2282 Target:5′-AACCCTAATTTTTTTTATTTAAGTACA-3′ (SEQ ID NO: 786)5′-AUUUUUUUUAUUUAAGUACAUUUUG-3′ (SEQ ID NO: 1114)3′-AUUAAAAAAAAUAAAUUCAUGUAAAAC-5′ (SEQ ID NO: 460) MYC-2287 Target:5′-TAATTTTTTTTATTTAAGTACATTTTG-3′ (SEQ ID NO: 787)5′-UAUUUAAGUACAUUUUGCUUUUUAA-3′ (SEQ ID NO: 1115)3′-AAAUAAAUUCAUGUAAAACGAAAAAUU-5′ (SEQ ID NO: 461) MYC-2295 Target:5′-TTTATTTAAGTACATTTTGCTTTTTAA-3′ (SEQ ID NO: 788)5′-AAGUACAUUUUGCUUUUUAAAGUUG-3′ (SEQ ID NO: 1116)3′-AAUUCAUGUAAAACGAAAAAUUUCAAC-5′ (SEQ ID NO: 462) MYC-2300 Target:5′-TTAAGTACATTTTGCTTTTTAAAGTTG-3′ (SEQ ID NO: 789)5′-AUUUUGCUUUUUAAAGUUGAUUUUU-3′ (SEQ ID NO: 1117)3′-UGUAAAACGAAAAAUUUCAACUAAAAA-5′ (SEQ ID NO: 463) MYC-2306 Target:5′-ACATTTTGCTTTTTAAAGTTGATTTTT-3′ (SEQ ID NO: 790)5′-CUUUUUAAAGUUGAUUUUUUUCUAU-3′ (SEQ ID NO: 1118)3′-ACGAAAAAUUUCAACUAAAAAAAGAUA-5′ (SEQ ID NO: 464) MYC-2312 Target:5′-TGCTTTTTAAAGTTGATTTTTTTCTAT-3′ (SEQ ID NO: 791)5′-UAUUGUUUUUAGAAAAAAUAAAAUA-3′ (SEQ ID NO: 1119)3′-AGAUAACAAAAAUCUUUUUUAUUUUAU-5′ (SEQ ID NO: 465) MYC-2334 Target:5′-TCTATTGTTTTTAGAAAAAATAAAATA-3′ (SEQ ID NO: 792)5′-UUUUUAGAAAAAAUAAAAUAACUGG-3′ (SEQ ID NO: 1120)3′-ACAAAAAUCUUUUUUAUUUUAUUGACC-5′ (SEQ ID NO: 466) MYC-2339 Target:5′-TGTTTTTAGAAAAAATAAAATAACTGG-3′ (SEQ ID NO: 793)5′-AAAAAUAAAAUAACUGGCAAAUAUA-3′ (SEQ ID NO: 1121)3′-CUUUUUUAUUUUAUUGACCGUUUAUAU-5′ (SEQ ID NO: 467) MYC-2347 Target:5′-GAAAAAATAAAATAACTGGCAAATATA-3′ (SEQ ID NO: 794)5′-AAUAACUGGCAAAUAUAUCAUUGAG-3′ (SEQ ID NO: 1122)3′-UUUUAUUGACCGUUUAUAUAGUAACUC-5′ (SEQ ID NO: 468) MYC-2355 Target:5′-AAAATAACTGGCAAATATATCATTGAG-3′ (SEQ ID NO: 795)5′-CAAAUAUAUCAUUGAGCCAAAUCUU-3′ (SEQ ID NO: 1123)3′-CCGUUUAUAUAGUAACUCGGUUUAGAA-5′ (SEQ ID NO: 469) MYC-2364 Target:5′-GGCAAATATATCATTGAGCCAAATCTT-3′ (SEQ ID NO: 796)5′-AUCAUUGAGCCAAAUCUUAAAAAAA-3′ (SEQ ID NO: 1124)3′-UAUAGUAACUCGGUUUAGAAUUUUUUU-5′ (SEQ ID NO: 470) MYC-2371 Target:5′-ATATCATTGAGCCAAATCTTAAAAAAA-3′ (SEQ ID NO: 797)5′-GAGCCAAAUCUUAAAAAAAAAAAAA-3′ (SEQ ID NO: 1125)3′-AACUCGGUUUAGAAUUUUUUUUUUUUU-5′ (SEQ ID NO: 471) MYC-2377 Target:5′-TTGAGCCAAATCTTAAAAAAAAAAAAA-3′ (SEQ ID NO: 798)5′-ACUCGCUGUAGUAAUUCCAGCGAGA-3′ (SEQ ID NO: 1126)3′-AUUGAGCGACAUCAUUAAGGUCGCUCU-5′ (SEQ ID NO: 472) MYC-188 Target:5′-TAACTCGCTGTAGTAATTCCAGCGAGA-3′ (SEQ ID NO: 799)5′-CUCGCUGUAGUAAUUCCAGCGAGAG-3′ (SEQ ID NO: 1127)3′-UUGAGCGACAUCAUUAAGGUCGCUCUC-5′ (SEQ ID NO: 473) MYC-189 Target:5′-AACTCGCTGTAGTAATTCCAGCGAGAG-3′ (SEQ ID NO: 800)5′-UCGCUGUAGUAAUUCCAGCGAGAGG-3′ (SEQ ID NO: 1128)3′-UGAGCGACAUCAUUAAGGUCGCUCUCC-5′ (SEQ ID NO: 474) MYC-190 Target:5′-ACTCGCTGTAGTAATTCCAGCGAGAGG-3′ (SEQ ID NO: 801)5′-CGCUGUAGUAAUUCCAGCGAGAGGC-3′ (SEQ ID NO: 1129)3′-GAGCGACAUCAUUAAGGUCGCUCUCCG-5′ (SEQ ID NO: 475) MYC-191 Target:5′-CTCGCTGTAGTAATTCCAGCGAGAGGC-3′ (SEQ ID NO: 802)5′-GCUGUAGUAAUUCCAGCGAGAGGCA-3′ (SEQ ID NO: 1130)3′-AGCGACAUCAUUAAGGUCGCUCUCCGU-5′ (SEQ ID NO: 476) MYC-192 Target:5′-TCGCTGTAGTAATTCCAGCGAGAGGCA-3′ (SEQ ID NO: 803)5′-CUGUAGUAAUUCCAGCGAGAGGCAG-3′ (SEQ ID NO: 1131)3′-GCGACAUCAUUAAGGUCGCUCUCCGUC-5′ (SEQ ID NO: 477) MYC-193 Target:5′-CGCTGTAGTAATTCCAGCGAGAGGCAG-3′ (SEQ ID NO: 804)5′-UGUAGUAAUUCCAGCGAGAGGCAGA-3′ (SEQ ID NO: 1132)3′-CGACAUCAUUAAGGUCGCUCUCCGUCU-5′ (SEQ ID NO: 478) MYC-194 Target:5′-GCTGTAGTAATTCCAGCGAGAGGCAGA-3′ (SEQ ID NO: 805)5′-GUAGUAAUUCCAGCGAGAGGCAGAG-3′ (SEQ ID NO: 1133)3′-GACAUCAUUAAGGUCGCUCUCCGUCUC-5′ (SEQ ID NO: 479) MYC-195 Target:5′-CTGTAGTAATTCCAGCGAGAGGCAGAG-3′ (SEQ ID NO: 806)5′-CUUCACCAACAGGAACUAUGACCUC-3′ (SEQ ID NO: 1134)3′-UCGAAGUGGUUGUCCUUGAUACUGGAG-5′ (SEQ ID NO: 480) MYC-612 Target:5′-AGCTTCACCAACAGGAACTATGACCTC-3′ (SEQ ID NO: 807)5′-UUCACCAACAGGAACUAUGACCUCG-3′ (SEQ ID NO: 1135)3′-CGAAGUGGUUGUCCUUGAUACUGGAGC-5′ (SEQ ID NO: 481) MYC-613 Target:5′-GCTTCACCAACAGGAACTATGACCTCG-3′ (SEQ ID NO: 808)5′-UCACCAACAGGAACUAUGACCUCGA-3′ (SEQ ID NO: 1136)3′-GAAGUGGUUGUCCUUGAUACUGGAGCU-5′ (SEQ ID NO: 482) MYC-614 Target:5′-CTTCACCAACAGGAACTATGACCTCGA-3′ (SEQ ID NO: 809)5′-CACCAACAGGAACUAUGACCUCGAC-3′ (SEQ ID NO: 1137)3′-AAGUGGUUGUCCUUGAUACUGGAGCUG-5′ (SEQ ID NO: 483) MYC-615 Target:5′-TTCACCAACAGGAACTATGACCTCGAC-3′ (SEQ ID NO: 810)5′-ACCAACAGGAACUAUGACCUCGACU-3′ (SEQ ID NO: 1138)3′-AGUGGUUGUCCUUGAUACUGGAGCUGA-5′ (SEQ ID NO: 484) MYC-616 Target:5′-TCACCAACAGGAACTATGACCTCGACT-3′ (SEQ ID NO: 811)5′-CCAACAGGAACUAUGACCUCGACUA-3′ (SEQ ID NO: 1139)3′-GUGGUUGUCCUUGAUACUGGAGCUGAU-5′ (SEQ ID NO: 485) MYC-617 Target:5′-CACCAACAGGAACTATGACCTCGACTA-3′ (SEQ ID NO: 812)5′-CAACAGGAACUAUGACCUCGACUAC-3′ (SEQ ID NO: 1140)3′-UGGUUGUCCUUGAUACUGGAGCUGAUG-5′ (SEQ ID NO: 486) MYC-618 Target:5′-ACCAACAGGAACTATGACCTCGACTAC-3′ (SEQ ID NO: 813)5′-AACAGGAACUAUGACCUCGACUACG-3′ (SEQ ID NO: 1141)3′-GGUUGUCCUUGAUACUGGAGCUGAUGC-5′ (SEQ ID NO: 487) MYC-619 Target:5′-CCAACAGGAACTATGACCTCGACTACG-3′ (SEQ ID NO: 814)5′-ACAGGAACUAUGACCUCGACUACGA-3′ (SEQ ID NO: 1142)3′-GUUGUCCUUGAUACUGGAGCUGAUGCU-5′ (SEQ ID NO: 488) MYC-620 Target:5′-CAACAGGAACTATGACCTCGACTACGA-3′ (SEQ ID NO: 815)5′-CAGGAACUAUGACCUCGACUACGAC-3′ (SEQ ID NO: 1143)3′-UUGUCCUUGAUACUGGAGCUGAUGCUG-5′ (SEQ ID NO: 489) MYC-621 Target:5′-AACAGGAACTATGACCTCGACTACGAC-3′ (SEQ ID NO: 816)5′-AGGAACUAUGACCUCGACUACGACU-3′ (SEQ ID NO: 1144)3′-UGUCCUUGAUACUGGAGCUGAUGCUGA-5′ (SEQ ID NO: 490) MYC-622 Target:5′-ACAGGAACTATGACCTCGACTACGACT-3′ (SEQ ID NO: 817)5′-GGAACUAUGACCUCGACUACGACUC-3′ (SEQ ID NO: 1145)3′-GUCCUUGAUACUGGAGCUGAUGCUGAG-5′ (SEQ ID NO: 491) MYC-623 Target:5′-CAGGAACTATGACCTCGACTACGACTC-3′ (SEQ ID NO: 818)5′-GAACUAUGACCUCGACUACGACUCG-3′ (SEQ ID NO: 1146)3′-UCCUUGAUACUGGAGCUGAUGCUGAGC-5′ (SEQ ID NO: 492) MYC-624 Target:5′-AGGAACTATGACCTCGACTACGACTCG-3′ (SEQ ID NO: 819)5′-AACUAUGACCUCGACUACGACUCGG-3′ (SEQ ID NO: 1147)3′-CCUUGAUACUGGAGCUGAUGCUGAGCC-5′ (SEQ ID NO: 493) MYC-625 Target:5′-GGAACTATGACCTCGACTACGACTCGG-3′ (SEQ ID NO: 820)5′-ACUAUGACCUCGACUACGACUCGGU-3′ (SEQ ID NO: 1148)3′-CUUGAUACUGGAGCUGAUGCUGAGCCA-5′ (SEQ ID NO: 494) MYC-626 Target:5′-GAACTATGACCTCGACTACGACTCGGT-3′ (SEQ ID NO: 821)5′-CUAUGACCUCGACUACGACUCGGUG-3′ (SEQ ID NO: 1149)3′-UUGAUACUGGAGCUGAUGCUGAGCCAC-5′ (SEQ ID NO: 495) MYC-627 Target:5′-AACTATGACCTCGACTACGACTCGGTG-3′ (SEQ ID NO: 822)5′-UAUGACCUCGACUACGACUCGGUGC-3′ (SEQ ID NO: 1150)3′-UGAUACUGGAGCUGAUGCUGAGCCACG-5′ (SEQ ID NO: 496) MYC-628 Target:5′-ACTATGACCTCGACTACGACTCGGTGC-3′ (SEQ ID NO: 823)5′-AUGACCUCGACUACGACUCGGUGCA-3′ (SEQ ID NO: 1151)3′-GAUACUGGAGCUGAUGCUGAGCCACGU-5′ (SEQ ID NO: 497) MYC-629 Target:5′-CTATGACCTCGACTACGACTCGGTGCA-3′ (SEQ ID NO: 824)5′-GAGGAUAUCUGGAAGAAAUUCGAGC-3′ (SEQ ID NO: 1152)3′-CGCUCCUAUAGACCUUCUUUAAGCUCG-5′ (SEQ ID NO: 498) MYC-733 Target:5′-GCGAGGATATCTGGAAGAAATTCGAGC-3′ (SEQ ID NO: 825)5′-AGGAUAUCUGGAAGAAAUUCGAGCU-3′ (SEQ ID NO: 1153)3′-GCUCCUAUAGACCUUCUUUAAGCUCGA-5′ (SEQ ID NO: 499) MYC-734 Target:5′-CGAGGATATCTGGAAGAAATTCGAGCT-3′ (SEQ ID NO: 826)5′-GGAUAUCUGGAAGAAAUUCGAGCUG-3′ (SEQ ID NO: 1154)3′-CUCCUAUAGACCUUCUUUAAGCUCGAC-5′ (SEQ ID NO: 500) MYC-735 Target:5′-GAGGATATCTGGAAGAAATTCGAGCTG-3′ (SEQ ID NO: 827)5′-GAUAUCUGGAAGAAAUUCGAGCUGC-3′ (SEQ ID NO: 1155)3′-UCCUAUAGACCUUCUUUAAGCUCGACG-5′ (SEQ ID NO: 501) MYC-736 Target:5′-AGGATATCTGGAAGAAATTCGAGCTGC-3′ (SEQ ID NO: 828)5′-AUAUCUGGAAGAAAUUCGAGCUGCU-3′ (SEQ ID NO: 1156)3′-CCUAUAGACCUUCUUUAAGCUCGACGA-5′ (SEQ ID NO: 502) MYC-737 Target:5′-GGATATCTGGAAGAAATTCGAGCTGCT-3′ (SEQ ID NO: 829)5′-UAUCUGGAAGAAAUUCGAGCUGCUG-3′ (SEQ ID NO: 1157)3′-CUAUAGACCUUCUUUAAGCUCGACGAC-5′ (SEQ ID NO: 503) MYC-738 Target:5′-GATATCTGGAAGAAATTCGAGCTGCTG-3′ (SEQ ID NO: 830)5′-AUCUGGAAGAAAUUCGAGCUGCUGC-3′ (SEQ ID NO: 1158)3′-UAUAGACCUUCUUUAAGCUCGACGACG-5′ (SEQ ID NO: 504) MYC-739 Target:5′-ATATCTGGAAGAAATTCGAGCTGCTGC-3′ (SEQ ID NO: 831)5′-UCUGGAAGAAAUUCGAGCUGCUGCC-3′ (SEQ ID NO: 1159)3′-AUAGACCUUCUUUAAGCUCGACGACGG-5′ (SEQ ID NO: 505) MYC-740 Target:5′-TATCTGGAAGAAATTCGAGCTGCTGCC-3′ (SEQ ID NO: 832)5′-CUGGAAGAAAUUCGAGCUGCUGCCC-3′ (SEQ ID NO: 1160)3′-UAGACCUUCUUUAAGCUCGACGACGGG-5′ (SEQ ID NO: 506) MYC-741 Target:5′-ATCTGGAAGAAATTCGAGCTGCTGCCC-3′ (SEQ ID NO: 833)5′-UGGAAGAAAUUCGAGCUGCUGCCCA-3′ (SEQ ID NO: 1161)3′-AGACCUUCUUUAAGCUCGACGACGGGU-5′ (SEQ ID NO: 507) MYC-742 Target:5′-TCTGGAAGAAATTCGAGCTGCTGCCCA-3′ (SEQ ID NO: 834)5′-GGAAGAAAUUCGAGCUGCUGCCCAC-3′ (SEQ ID NO: 1162)3′-GACCUUCUUUAAGCUCGACGACGGGUG-5′ (SEQ ID NO: 508) MYC-743 Target:5′-CTGGAAGAAATTCGAGCTGCTGCCCAC-3′ (SEQ ID NO: 835)5′-AGCCGCCGCUCCGGGCUCUGCUCGC-3′ (SEQ ID NO: 1163)3′-GAUCGGCGGCGAGGCCCGAGACGAGCG-5′ (SEQ ID NO: 509) MYC-784 Target:5′-CTAGCCGCCGCTCCGGGCTCTGCTCGC-3′ (SEQ ID NO: 836)5′-GCCGCCGCUCCGGGCUCUGCUCGCC-3′ (SEQ ID NO: 1164)3′-AUCGGCGGCGAGGCCCGAGACGAGCGG-5′ (SEQ ID NO: 510) MYC-785 Target:5′-TAGCCGCCGCTCCGGGCTCTGCTCGCC-3′ (SEQ ID NO: 837)5′-CCGCCGCUCCGGGCUCUGCUCGCCC-3′ (SEQ ID NO: 1165)3′-UCGGCGGCGAGGCCCGAGACGAGCGGG-5′ (SEQ ID NO: 511) MYC-786 Target:5′-AGCCGCCGCTCCGGGCTCTGCTCGCCC-3′ (SEQ ID NO: 838)5′-CGCCGCUCCGGGCUCUGCUCGCCCU-3′ (SEQ ID NO: 1166)3′-CGGCGGCGAGGCCCGAGACGAGCGGGA-5′ (SEQ ID NO: 512) MYC-787 Target:5′-GCCGCCGCTCCGGGCTCTGCTCGCCCT-3′ (SEQ ID NO: 839)5′-GCCGCUCCGGGCUCUGCUCGCCCUC-3′ (SEQ ID NO: 1167)3′-GGCGGCGAGGCCCGAGACGAGCGGGAG-5′ (SEQ ID NO: 513) MYC-788 Target:5′-CCGCCGCTCCGGGCTCTGCTCGCCCTC-3′ (SEQ ID NO: 840)5′-GGAGGAGACAUGGUGAACCAGAGUU-3′ (SEQ ID NO: 1168)3′-ACCCUCCUCUGUACCACUUGGUCUCAA-5′ (SEQ ID NO: 514) MYC-913 Target:5′-TGGGAGGAGACATGGTGAACCAGAGTT-3′ (SEQ ID NO: 841)5′-GAGGAGACAUGGUGAACCAGAGUUU-3′ (SEQ ID NO: 1169)3′-CCCUCCUCUGUACCACUUGGUCUCAAA-5′ (SEQ ID NO: 515) MYC-914 Target:5′-GGGAGGAGACATGGTGAACCAGAGTTT-3′ (SEQ ID NO: 842)5′-AGGAGACAUGGUGAACCAGAGUUUC-3′ (SEQ ID NO: 1170)3′-CCUCCUCUGUACCACUUGGUCUCAAAG-5′ (SEQ ID NO: 516) MYC-915 Target:5′-GGAGGAGACATGGTGAACCAGAGTTTC-3′ (SEQ ID NO: 843)5′-GGAGACAUGGUGAACCAGAGUUUCA-3′ (SEQ ID NO: 1171)3′-CUCCUCUGUACCACUUGGUCUCAAAGU-5′ (SEQ ID NO: 517) MYC-916 Target:5′-GAGGAGACATGGTGAACCAGAGTTTCA-3′ (SEQ ID NO: 844)5′-GAGACAUGGUGAACCAGAGUUUCAU-3′ (SEQ ID NO: 1172)3′-UCCUCUGUACCACUUGGUCUCAAAGUA-5′ (SEQ ID NO: 518) MYC-917 Target:5′-AGGAGACATGGTGAACCAGAGTTTCAT-3′ (SEQ ID NO: 845)5′-GACGACGAGACCUUCAUCAAAAACA-3′ (SEQ ID NO: 1173)3′-GCCUGCUGCUCUGGAAGUAGUUUUUGU-5′ (SEQ ID NO: 519) MYC-952 Target:5′-CGGACGACGAGACCTTCATCAAAAACA-3′ (SEQ ID NO: 846)5′-ACGACGAGACCUUCAUCAAAAACAU-3′ (SEQ ID NO: 1174)3′-CCUGCUGCUCUGGAAGUAGUUUUUGUA-5′ (SEQ ID NO: 520) MYC-953 Target:5′-GGACGACGAGACCTTCATCAAAAACAT-3′ (SEQ ID NO: 847)5′-AACAUCAUCAUCCAGGACUGUAUGU-3′ (SEQ ID NO: 1175)3′-UUUUGUAGUAGUAGGUCCUGACAUACA-5′ (SEQ ID NO: 521) MYC-973 Target:5′-AAAACATCATCATCCAGGACTGTATGT-3′ (SEQ ID NO: 848)5′-ACAUCAUCAUCCAGGACUGUAUGUG-3′ (SEQ ID NO: 1176)3′-UUUGUAGUAGUAGGUCCUGACAUACAC-5′ (SEQ ID NO: 522) MYC-974 Target:5′-AAACATCATCATCCAGGACTGTATGTG-3′ (SEQ ID NO: 849)5′-CAUCAUCAUCCAGGACUGUAUGUGG-3′ (SEQ ID NO: 1177)3′-UUGUAGUAGUAGGUCCUGACAUACACC-5′ (SEQ ID NO: 523) MYC-975 Target:5′-AACATCATCATCCAGGACTGTATGTGG-3′ (SEQ ID NO: 850)5′-AUCAUCAUCCAGGACUGUAUGUGGA-3′ (SEQ ID NO: 1178)3′-UGUAGUAGUAGGUCCUGACAUACACCU-5′ (SEQ ID NO: 524) MYC-976 Target:5′-ACATCATCATCCAGGACTGTATGTGGA-3′ (SEQ ID NO: 851)5′-UCAUCAUCCAGGACUGUAUGUGGAG-3′ (SEQ ID NO: 1179)3′-GUAGUAGUAGGUCCUGACAUACACCUC-5′ (SEQ ID NO: 525) MYC-977 Target:5′-CATCATCATCCAGGACTGTATGTGGAG-3′ (SEQ ID NO: 852)5′-CAUCAUCCAGGACUGUAUGUGGAGC-3′ (SEQ ID NO: 1180)3′-UAGUAGUAGGUCCUGACAUACACCUCG-5′ (SEQ ID NO: 526) MYC-978 Target:5′-ATCATCATCCAGGACTGTATGTGGAGC-3′ (SEQ ID NO: 853)5′-AUCAUCCAGGACUGUAUGUGGAGCG-3′ (SEQ ID NO: 1181)3′-AGUAGUAGGUCCUGACAUACACCUCGC-5′ (SEQ ID NO: 527) MYC-979 Target:5′-TCATCATCCAGGACTGTATGTGGAGCG-3′ (SEQ ID NO: 854)5′-UCAUCCAGGACUGUAUGUGGAGCGG-3′ (SEQ ID NO: 1182)3′-GUAGUAGGUCCUGACAUACACCUCGCC-5′ (SEQ ID NO: 528) MYC-980 Target:5′-CATCATCCAGGACTGTATGTGGAGCGG-3′ (SEQ ID NO: 855)5′-CAUCCAGGACUGUAUGUGGAGCGGC-3′ (SEQ ID NO: 1183)3′-UAGUAGGUCCUGACAUACACCUCGCCG-5′ (SEQ ID NO: 529) MYC-981 Target:5′-ATCATCCAGGACTGTATGTGGAGCGGC-3′ (SEQ ID NO: 856)5′-AUCCAGGACUGUAUGUGGAGCGGCU-3′ (SEQ ID NO: 1184)3′-AGUAGGUCCUGACAUACACCUCGCCGA-5′ (SEQ ID NO: 530) MYC-982 Target:5′-TCATCCAGGACTGTATGTGGAGCGGCT-3′ (SEQ ID NO: 857)5′-UCCAGGACUGUAUGUGGAGCGGCUU-3′ (SEQ ID NO: 1185)3′-GUAGGUCCUGACAUACACCUCGCCGAA-5′ (SEQ ID NO: 531) MYC-983 Target:5′-CATCCAGGACTGTATGTGGAGCGGCTT-3′ (SEQ ID NO: 858)5′-CCAGGACUGUAUGUGGAGCGGCUUC-3′ (SEQ ID NO: 1186)3′-UAGGUCCUGACAUACACCUCGCCGAAG-5′ (SEQ ID NO: 532) MYC-984 Target:5′-ATCCAGGACTGTATGTGGAGCGGCTTC-3′ (SEQ ID NO: 859)5′-CAGGACUGUAUGUGGAGCGGCUUCU-3′ (SEQ ID NO: 1187)3′-AGGUCCUGACAUACACCUCGCCGAAGA-5′ (SEQ ID NO: 533) MYC-985 Target:5′-TCCAGGACTGTATGTGGAGCGGCTTCT-3′ (SEQ ID NO: 860)5′-AGGACUGUAUGUGGAGCGGCUUCUC-3′ (SEQ ID NO: 1188)3′-GGUCCUGACAUACACCUCGCCGAAGAG-5′ (SEQ ID NO: 534) MYC-986 Target:5′-CCAGGACTGTATGTGGAGCGGCTTCTC-3′ (SEQ ID NO: 861)5′-GAGAAGCUGGCCUCCUACCAGGCUG-3′ (SEQ ID NO: 1189)3′-GUCUCUUCGACCGGAGGAUGGUCCGAC-5′ (SEQ ID NO: 535) MYC-1033 Target:5′-CAGAGAAGCTGGCCTCCTACCAGGCTG-3′ (SEQ ID NO: 862)5′-AGAAGCUGGCCUCCUACCAGGCUGC-3′ (SEQ ID NO: 1190)3′-UCUCUUCGACCGGAGGAUGGUCCGACG-5′ (SEQ ID NO: 536) MYC-1034 Target:5′-AGAGAAGCTGGCCTCCTACCAGGCTGC-3′ (SEQ ID NO: 863)5′-GAAGCUGGCCUCCUACCAGGCUGCG-3′ (SEQ ID NO: 1191)3′-CUCUUCGACCGGAGGAUGGUCCGACGC-5′ (SEQ ID NO: 537) MYC-1035 Target:5′-GAGAAGCTGGCCTCCTACCAGGCTGCG-3′ (SEQ ID NO: 864)5′-AAGCUGGCCUCCUACCAGGCUGCGC-3′ (SEQ ID NO: 1192)3′-UCUUCGACCGGAGGAUGGUCCGACGCG-5′ (SEQ ID NO: 538) MYC-1036 Target:5′-AGAAGCTGGCCTCCTACCAGGCTGCGC-3′ (SEQ ID NO: 865)5′-AGCUGGCCUCCUACCAGGCUGCGCG-3′ (SEQ ID NO: 1193)3′-CUUCGACCGGAGGAUGGUCCGACGCGC-5′ (SEQ ID NO: 539) MYC-1037 Target:5′-GAAGCTGGCCTCCTACCAGGCTGCGCG-3′ (SEQ ID NO: 866)5′-GCUGGCCUCCUACCAGGCUGCGCGC-3′ (SEQ ID NO: 1194)3′-UUCGACCGGAGGAUGGUCCGACGCGCG-5′ (SEQ ID NO: 540) MYC-1038 Target:5′-AAGCTGGCCTCCTACCAGGCTGCGCGC-3′ (SEQ ID NO: 867)5′-CUGGCCUCCUACCAGGCUGCGCGCA-3′ (SEQ ID NO: 1195)3′-UCGACCGGAGGAUGGUCCGACGCGCGU-5′ (SEQ ID NO: 541) MYC-1039 Target:5′-AGCTGGCCTCCTACCAGGCTGCGCGCA-3′ (SEQ ID NO: 868)5′-UGGCCUCCUACCAGGCUGCGCGCAA-3′ (SEQ ID NO: 1196)3′-CGACCGGAGGAUGGUCCGACGCGCGUU-5′ (SEQ ID NO: 542) MYC-1040 Target:5′-GCTGGCCTCCTACCAGGCTGCGCGCAA-3′ (SEQ ID NO: 869)5′-GGCCUCCUACCAGGCUGCGCGCAAA-3′ (SEQ ID NO: 1197)3′-GACCGGAGGAUGGUCCGACGCGCGUUU-5′ (SEQ ID NO: 543) MYC-1041 Target:5′-CTGGCCTCCTACCAGGCTGCGCGCAAA-3′ (SEQ ID NO: 870)5′-GCCUCCUACCAGGCUGCGCGCAAAG-3′ (SEQ ID NO: 1198)3′-ACCGGAGGAUGGUCCGACGCGCGUUUC-5′ (SEQ ID NO: 544) MYC-1042 Target:5′-TGGCCTCCTACCAGGCTGCGCGCAAAG-3′ (SEQ ID NO: 871)5′-CCUCCUACCAGGCUGCGCGCAAAGA-3′ (SEQ ID NO: 1199)3′-CCGGAGGAUGGUCCGACGCGCGUUUCU-5′ (SEQ ID NO: 545) MYC-1043 Target:5′-GGCCTCCTACCAGGCTGCGCGCAAAGA-3′ (SEQ ID NO: 872)5′-CUCCUACCAGGCUGCGCGCAAAGAC-3′ (SEQ ID NO: 1200)3′-CGGAGGAUGGUCCGACGCGCGUUUCUG-5′ (SEQ ID NO: 546) MYC-1044 Target:5′-GCCTCCTACCAGGCTGCGCGCAAAGAC-3′ (SEQ ID NO: 873)5′-UCCUACCAGGCUGCGCGCAAAGACA-3′ (SEQ ID NO: 1201)3′-GGAGGAUGGUCCGACGCGCGUUUCUGU-5′ (SEQ ID NO: 547) MYC-1045 Target:5′-CCTCCTACCAGGCTGCGCGCAAAGACA-3′ (SEQ ID NO: 874)5′-CCUACCAGGCUGCGCGCAAAGACAG-3′ (SEQ ID NO: 1202)3′-GAGGAUGGUCCGACGCGCGUUUCUGUC-5′ (SEQ ID NO: 548) MYC-1046 Target:5′-CTCCTACCAGGCTGCGCGCAAAGACAG-3′ (SEQ ID NO: 875)5′-CUACCAGGCUGCGCGCAAAGACAGC-3′ (SEQ ID NO: 1203)3′-AGGAUGGUCCGACGCGCGUUUCUGUCG-5′ (SEQ ID NO: 549) MYC-1047 Target:5′-TCCTACCAGGCTGCGCGCAAAGACAGC-3′ (SEQ ID NO: 876)5′-UACCAGGCUGCGCGCAAAGACAGCG-3′ (SEQ ID NO: 1204)3′-GGAUGGUCCGACGCGCGUUUCUGUCGC-5′ (SEQ ID NO: 550) MYC-1048 Target:5′-CCTACCAGGCTGCGCGCAAAGACAGCG-3′ (SEQ ID NO: 877)5′-ACCAGGCUGCGCGCAAAGACAGCGG-3′ (SEQ ID NO: 1205)3′-GAUGGUCCGACGCGCGUUUCUGUCGCC-5′ (SEQ ID NO: 551) MYC-1049 Target:5′-CTACCAGGCTGCGCGCAAAGACAGCGG-3′ (SEQ ID NO: 878)5′-CCAGGCUGCGCGCAAAGACAGCGGC-3′ (SEQ ID NO: 1206)3′-AUGGUCCGACGCGCGUUUCUGUCGCCG-5′ (SEQ ID NO: 552) MYC-1050 Target:5′-TACCAGGCTGCGCGCAAAGACAGCGGC-3′ (SEQ ID NO: 879)5′-CAGGCUGCGCGCAAAGACAGCGGCA-3′ (SEQ ID NO: 1207)3′-UGGUCCGACGCGCGUUUCUGUCGCCGU-5′ (SEQ ID NO: 553) MYC-1051 Target:5′-ACCAGGCTGCGCGCAAAGACAGCGGCA-3′ (SEQ ID NO: 880)5′-AGGCUGCGCGCAAAGACAGCGGCAG-3′ (SEQ ID NO: 1208)3′-GGUCCGACGCGCGUUUCUGUCGCCGUC-5′ (SEQ ID NO: 554) MYC-1052 Target:5′-CCAGGCTGCGCGCAAAGACAGCGGCAG-3′ (SEQ ID NO: 881)5′-GGCUGCGCGCAAAGACAGCGGCAGC-3′ (SEQ ID NO: 1209)3′-GUCCGACGCGCGUUUCUGUCGCCGUCG-5′ (SEQ ID NO: 555) MYC-1053 Target:5′-CAGGCTGCGCGCAAAGACAGCGGCAGC-3′ (SEQ ID NO: 882)5′-CACAGCGUCUGCUCCACCUCCAGCU-3′ (SEQ ID NO: 1210)3′-CGGUGUCGCAGACGAGGUGGAGGUCGA-5′ (SEQ ID NO: 556) MYC-1096 Target:5′-GCCACAGCGTCTGCTCCACCTCCAGCT-3′ (SEQ ID NO: 883)5′-ACAGCGUCUGCUCCACCUCCAGCUU-3′ (SEQ ID NO: 1211)3′-GGUGUCGCAGACGAGGUGGAGGUCGAA-5′ (SEQ ID NO: 557) MYC-1097 Target:5′-CCACAGCGTCTGCTCCACCTCCAGCTT-3′ (SEQ ID NO: 884)5′-CAGCGUCUGCUCCACCUCCAGCUUG-3′ (SEQ ID NO: 1212)3′-GUGUCGCAGACGAGGUGGAGGUCGAAC-5′ (SEQ ID NO: 558) MYC-1098 Target:5′-CACAGCGTCTGCTCCACCTCCAGCTTG-3′ (SEQ ID NO: 885)5′-AGCGUCUGCUCCACCUCCAGCUUGU-3′ (SEQ ID NO: 1213)3′-UGUCGCAGACGAGGUGGAGGUCGAACA-5′ (SEQ ID NO: 559) MYC-1099 Target:5′-ACAGCGTCTGCTCCACCTCCAGCTTGT-3′ (SEQ ID NO: 886)5′-GCGUCUGCUCCACCUCCAGCUUGUA-3′ (SEQ ID NO: 1214)3′-GUCGCAGACGAGGUGGAGGUCGAACAU-5′ (SEQ ID NO: 560) MYC-1100 Target:5′-CAGCGTCTGCTCCACCTCCAGCTTGTA-3′ (SEQ ID NO: 887)5′-CGUCUGCUCCACCUCCAGCUUGUAC-3′ (SEQ ID NO: 1215)3′-UCGCAGACGAGGUGGAGGUCGAACAUG-5′ (SEQ ID NO: 561) MYC-1101 Target:5′-AGCGTCTGCTCCACCTCCAGCTTGTAC-3′ (SEQ ID NO: 888)5′-CUCAACGACAGCAGCUCGCCCAAGU-3′ (SEQ ID NO: 1216)3′-GAGAGUUGCUGUCGUCGAGCGGGUUCA-5′ (SEQ ID NO: 562) MYC-1189 Target:5′-CTCTCAACGACAGCAGCTCGCCCAAGT-3′ (SEQ ID NO: 889)5′-UCAACGACAGCAGCUCGCCCAAGUC-3′ (SEQ ID NO: 1217)3′-AGAGUUGCUGUCGUCGAGCGGGUUCAG-5′ (SEQ ID NO: 563) MYC-1190 Target:5′-TCTCAACGACAGCAGCTCGCCCAAGTC-3′ (SEQ ID NO: 890)5′-CAACGACAGCAGCUCGCCCAAGUCC-3′ (SEQ ID NO: 1218)3′-GAGUUGCUGUCGUCGAGCGGGUUCAGG-5′ (SEQ ID NO: 564) MYC-1191 Target:5′-CTCAACGACAGCAGCTCGCCCAAGTCC-3′ (SEQ ID NO: 891)5′-AACGACAGCAGCUCGCCCAAGUCCU-3′ (SEQ ID NO: 1219)3′-AGUUGCUGUCGUCGAGCGGGUUCAGGA-5′ (SEQ ID NO: 565) MYC-1192 Target:5′-TCAACGACAGCAGCTCGCCCAAGTCCT-3′ (SEQ ID NO: 892)5′-ACGACAGCAGCUCGCCCAAGUCCUG-3′ (SEQ ID NO: 1220)3′-GUUGCUGUCGUCGAGCGGGUUCAGGAC-5′ (SEQ ID NO: 566) MYC-1193 Target:5′-CAACGACAGCAGCTCGCCCAAGTCCTG-3′ (SEQ ID NO: 893)5′-CAUGAGGAGACACCGCCCACCACCA-3′ (SEQ ID NO: 1221)3′-AGGUACUCCUCUGUGGCGGGUGGUGGU-5′ (SEQ ID NO: 567) MYC-1315 Target:5′-TCCATGAGGAGACACCGCCCACCACCA-3′ (SEQ ID NO: 894)5′-AUGAGGAGACACCGCCCACCACCAG-3′ (SEQ ID NO: 1222)3′-GGUACUCCUCUGUGGCGGGUGGUGGUC-5′ (SEQ ID NO: 568) MYC-1316 Target:5′-CCATGAGGAGACACCGCCCACCACCAG-3′ (SEQ ID NO: 895)5′-UGAGGAGACACCGCCCACCACCAGC-3′ (SEQ ID NO: 1223)3′-GUACUCCUCUGUGGCGGGUGGUGGUCG-5′ (SEQ ID NO: 569) MYC-1317 Target:5′-CATGAGGAGACACCGCCCACCACCAGC-3′ (SEQ ID NO: 896)5′-GAGGAGACACCGCCCACCACCAGCA-3′ (SEQ ID NO: 1224)3′-UACUCCUCUGUGGCGGGUGGUGGUCGU-5′ (SEQ ID NO: 570) MYC-1318 Target:5′-ATGAGGAGACACCGCCCACCACCAGCA-3′ (SEQ ID NO: 897)5′-AGGAGACACCGCCCACCACCAGCAG-3′ (SEQ ID NO: 1225)3′-ACUCCUCUGUGGCGGGUGGUGGUCGUC-5′ (SEQ ID NO: 571) MYC-1319 Target:5′-TGAGGAGACACCGCCCACCACCAGCAG-3′ (SEQ ID NO: 898)5′-GGAGACACCGCCCACCACCAGCAGC-3′ (SEQ ID NO: 1226)3′-CUCCUCUGUGGCGGGUGGUGGUCGUCG-5′ (SEQ ID NO: 572) MYC-1320 Target:5′-GAGGAGACACCGCCCACCACCAGCAGC-3′ (SEQ ID NO: 899)5′-GAGACACCGCCCACCACCAGCAGCG-3′ (SEQ ID NO: 1227)3′-UCCUCUGUGGCGGGUGGUGGUCGUCGC-5′ (SEQ ID NO: 573) MYC-1321 Target:5′-AGGAGACACCGCCCACCACCAGCAGCG-3′ (SEQ ID NO: 900)5′-AGACACCGCCCACCACCAGCAGCGA-3′ (SEQ ID NO: 1228)3′-CCUCUGUGGCGGGUGGUGGUCGUCGCU-5′ (SEQ ID NO: 574) MYC-1322 Target:5′-GGAGACACCGCCCACCACCAGCAGCGA-3′ (SEQ ID NO: 901)5′-GACACCGCCCACCACCAGCAGCGAC-3′ (SEQ ID NO: 1229)3′-CUCUGUGGCGGGUGGUGGUCGUCGCUG-5′ (SEQ ID NO: 575) MYC-1323 Target:5′-GAGACACCGCCCACCACCAGCAGCGAC-3′ (SEQ ID NO: 902)5′-ACACCGCCCACCACCAGCAGCGACU-3′ (SEQ ID NO: 1230)3′-UCUGUGGCGGGUGGUGGUCGUCGCUGA-5′ (SEQ ID NO: 576) MYC-1324 Target:5′-AGACACCGCCCACCACCAGCAGCGACT-3′ (SEQ ID NO: 903)5′-CACCGCCCACCACCAGCAGCGACUC-3′ (SEQ ID NO: 1231)3′-CUGUGGCGGGUGGUGGUCGUCGCUGAG-5′ (SEQ ID NO: 577) MYC-1325 Target:5′-GACACCGCCCACCACCAGCAGCGACTC-3′ (SEQ ID NO: 904)5′-ACCGCCCACCACCAGCAGCGACUCU-3′ (SEQ ID NO: 1232)3′-UGUGGCGGGUGGUGGUCGUCGCUGAGA-5′ (SEQ ID NO: 578) MYC-1326 Target:5′-ACACCGCCCACCACCAGCAGCGACTCT-3′ (SEQ ID NO: 905)5′-CCGCCCACCACCAGCAGCGACUCUG-3′ (SEQ ID NO: 1233)3′-GUGGCGGGUGGUGGUCGUCGCUGAGAC-5′ (SEQ ID NO: 579) MYC-1327 Target:5′-CACCGCCCACCACCAGCAGCGACTCTG-3′ (SEQ ID NO: 906)5′-CGCCCACCACCAGCAGCGACUCUGA-3′ (SEQ ID NO: 1234)3′-UGGCGGGUGGUGGUCGUCGCUGAGACU-5′ (SEQ ID NO: 580) MYC-1328 Target:5′-ACCGCCCACCACCAGCAGCGACTCTGA-3′ (SEQ ID NO: 907)5′-GCCCACCACCAGCAGCGACUCUGAG-3′ (SEQ ID NO: 1235)3′-GGCGGGUGGUGGUCGUCGCUGAGACUC-5′ (SEQ ID NO: 581) MYC-1329 Target:5′-CCGCCCACCACCAGCAGCGACTCTGAG-3′ (SEQ ID NO: 908)5′-CCCACCACCAGCAGCGACUCUGAGG-3′ (SEQ ID NO: 1236)3′-GCGGGUGGUGGUCGUCGCUGAGACUCC-5′ (SEQ ID NO: 582) MYC-1330 Target:5′-CGCCCACCACCAGCAGCGACTCTGAGG-3′ (SEQ ID NO: 909)5′-CCACCACCAGCAGCGACUCUGAGGA-3′ (SEQ ID NO: 1237)3′-CGGGUGGUGGUCGUCGCUGAGACUCCU-5′ (SEQ ID NO: 583) MYC-1331 Target:5′-GCCCACCACCAGCAGCGACTCTGAGGA-3′ (SEQ ID NO: 910)5′-CACCACCAGCAGCGACUCUGAGGAG-3′ (SEQ ID NO: 1238)3′-GGGUGGUGGUCGUCGCUGAGACUCCUC-5′ (SEQ ID NO: 584) MYC-1332 Target:5′-CCCACCACCAGCAGCGACTCTGAGGAG-3′ (SEQ ID NO: 911)5′-ACCACCAGCAGCGACUCUGAGGAGG-3′ (SEQ ID NO: 1239)3′-GGUGGUGGUCGUCGCUGAGACUCCUCC-5′ (SEQ ID NO: 585) MYC-1333 Target:5′-CCACCACCAGCAGCGACTCTGAGGAGG-3′ (SEQ ID NO: 912)5′-CCACCAGCAGCGACUCUGAGGAGGA-3′ (SEQ ID NO: 1240)3′-GUGGUGGUCGUCGCUGAGACUCCUCCU-5′ (SEQ ID NO: 586) MYC-1334 Target:5′-CACCACCAGCAGCGACTCTGAGGAGGA-3′ (SEQ ID NO: 913)5′-CAAGAAGAUGAGGAAGAAAUCGAUG-3′ (SEQ ID NO: 1241)3′-UUGUUCUUCUACUCCUUCUUUAGCUAC-5′ (SEQ ID NO: 587) MYC-1360 Target:5′-AACAAGAAGATGAGGAAGAAATCGATG-3′ (SEQ ID NO: 914)5′-AAGAAGAUGAGGAAGAAAUCGAUGU-3′ (SEQ ID NO: 1242)3′-UGUUCUUCUACUCCUUCUUUAGCUACA-5′ (SEQ ID NO: 588) MYC-1361 Target:5′-ACAAGAAGATGAGGAAGAAATCGATGT-3′ (SEQ ID NO: 915)5′-GAGGCCACAGCAAACCUCCUCACAG-3′ (SEQ ID NO: 1243)3′-ACCUCCGGUGUCGUUUGGAGGAGUGUC-5′ (SEQ ID NO: 589) MYC-1448 Target:5′-TGGAGGCCACAGCAAACCTCCTCACAG-3′ (SEQ ID NO: 916)5′-CACAGCCCACUGGUCCUCAAGAGGU-3′ (SEQ ID NO: 1244)3′-GAGUGUCGGGUGACCAGGAGUUCUCCA-5′ (SEQ ID NO: 590) MYC-1468 Target:5′-CTCACAGCCCACTGGTCCTCAAGAGGT-3′ (SEQ ID NO: 917)5′-ACAGCCCACUGGUCCUCAAGAGGUG-3′ (SEQ ID NO: 1245)3′-AGUGUCGGGUGACCAGGAGUUCUCCAC-5′ (SEQ ID NO: 591) MYC-1469 Target:5′-TCACAGCCCACTGGTCCTCAAGAGGTG-3′ (SEQ ID NO: 918)5′-CAGCCCACUGGUCCUCAAGAGGUGC-3′ (SEQ ID NO: 1246)3′-GUGUCGGGUGACCAGGAGUUCUCCACG-5′ (SEQ ID NO: 592) MYC-1470 Target:5′-CACAGCCCACTGGTCCTCAAGAGGTGC-3′ (SEQ ID NO: 919)5′-AGCCCACUGGUCCUCAAGAGGUGCC-3′ (SEQ ID NO: 1247)3′-UGUCGGGUGACCAGGAGUUCUCCACGG-5′ (SEQ ID NO: 593) MYC-1471 Target:5′-ACAGCCCACTGGTCCTCAAGAGGTGCC-3′ (SEQ ID NO: 920)5′-GCCCACUGGUCCUCAAGAGGUGCCA-3′ (SEQ ID NO: 1248)3′-GUCGGGUGACCAGGAGUUCUCCACGGU-5′ (SEQ ID NO: 594) MYC-1472 Target:5′-CAGCCCACTGGTCCTCAAGAGGTGCCA-3′ (SEQ ID NO: 921)5′-CCCACUGGUCCUCAAGAGGUGCCAC-3′ (SEQ ID NO: 1249)3′-UCGGGUGACCAGGAGUUCUCCACGGUG-5′ (SEQ ID NO: 595) MYC-1473 Target:5′-AGCCCACTGGTCCTCAAGAGGTGCCAC-3′ (SEQ ID NO: 922)5′-CCACUGGUCCUCAAGAGGUGCCACG-3′ (SEQ ID NO: 1250)3′-CGGGUGACCAGGAGUUCUCCACGGUGC-5′ (SEQ ID NO: 596) MYC-1474 Target:5′-GCCCACTGGTCCTCAAGAGGTGCCACG-3′ (SEQ ID NO: 923)5′-CACUGGUCCUCAAGAGGUGCCACGU-3′ (SEQ ID NO: 1251)3′-GGGUGACCAGGAGUUCUCCACGGUGCA-5′ (SEQ ID NO: 597) MYC-1475 Target:5′-CCCACTGGTCCTCAAGAGGTGCCACGT-3′ (SEQ ID NO: 924)5′-ACUGGUCCUCAAGAGGUGCCACGUC-3′ (SEQ ID NO: 1252)3′-GGUGACCAGGAGUUCUCCACGGUGCAG-5′ (SEQ ID NO: 598) MYC-1476 Target:5′-CCACTGGTCCTCAAGAGGTGCCACGTC-3′ (SEQ ID NO: 925)5′-CUGGUCCUCAAGAGGUGCCACGUCU-3′ (SEQ ID NO: 1253)3′-GUGACCAGGAGUUCUCCACGGUGCAGA-5′ (SEQ ID NO: 599) MYC-1477 Target:5′-CACTGGTCCTCAAGAGGTGCCACGTCT-3′ (SEQ ID NO: 926)5′-UGGUCCUCAAGAGGUGCCACGUCUC-3′ (SEQ ID NO: 1254)3′-UGACCAGGAGUUCUCCACGGUGCAGAG-5′ (SEQ ID NO: 600) MYC-1478 Target:5′-ACTGGTCCTCAAGAGGTGCCACGTCTC-3′ (SEQ ID NO: 927)5′-GGUCCUCAAGAGGUGCCACGUCUCC-3′ (SEQ ID NO: 1255)3′-GACCAGGAGUUCUCCACGGUGCAGAGG-5′ (SEQ ID NO: 601) MYC-1479 Target:5′-CTGGTCCTCAAGAGGTGCCACGTCTCC-3′ (SEQ ID NO: 928)5′-GUCCUCAAGAGGUGCCACGUCUCCA-3′ (SEQ ID NO: 1256)3′-ACCAGGAGUUCUCCACGGUGCAGAGGU-5′ (SEQ ID NO: 602) MYC-1480 Target:5′-TGGTCCTCAAGAGGTGCCACGTCTCCA-3′ (SEQ ID NO: 929)5′-UCCUCAAGAGGUGCCACGUCUCCAC-3′ (SEQ ID NO: 1257)3′-CCAGGAGUUCUCCACGGUGCAGAGGUG-5′ (SEQ ID NO: 603) MYC-1481 Target:5′-GGTCCTCAAGAGGTGCCACGTCTCCAC-3′ (SEQ ID NO: 930)5′-CCUCAAGAGGUGCCACGUCUCCACA-3′ (SEQ ID NO: 1258)3′-CAGGAGUUCUCCACGGUGCAGAGGUGU-5′ (SEQ ID NO: 604) MYC-1482 Target:5′-GTCCTCAAGAGGTGCCACGTCTCCACA-3′ (SEQ ID NO: 931)5′-CUCAAGAGGUGCCACGUCUCCACAC-3′ (SEQ ID NO: 1259)3′-AGGAGUUCUCCACGGUGCAGAGGUGUG-5′ (SEQ ID NO: 605) MYC-1483 Target:5′-TCCTCAAGAGGTGCCACGTCTCCACAC-3′ (SEQ ID NO: 932)5′-AGCUUUUUUGCCCUGCGUGACCAGA-3′ (SEQ ID NO: 1260)3′-CCUCGAAAAAACGGGACGCACUGGUCU-5′ (SEQ ID NO: 606) MYC-1711 Target:5′-GGAGCTTTTTTGCCCTGCGTGACCAGA-3′ (SEQ ID NO: 933)5′-GCUUUUUUGCCCUGCGUGACCAGAU-3′ (SEQ ID NO: 1261)3′-CUCGAAAAAACGGGACGCACUGGUCUA-5′ (SEQ ID NO: 607) MYC-1712 Target:5′-GAGCTTTTTTGCCCTGCGTGACCAGAT-3′ (SEQ ID NO: 934)5′-CUUUUUUGCCCUGCGUGACCAGAUC-3′ (SEQ ID NO: 1262)3′-UCGAAAAAACGGGACGCACUGGUCUAG-5′ (SEQ ID NO: 608) MYC-1713 Target:5′-AGCTTTTTTGCCCTGCGTGACCAGATC-3′ (SEQ ID NO: 935)5′-UUUUUUGCCCUGCGUGACCAGAUCC-3′ (SEQ ID NO: 1263)3′-CGAAAAAACGGGACGCACUGGUCUAGG-5′ (SEQ ID NO: 609) MYC-1714 Target:5′-GCTTTTTTGCCCTGCGTGACCAGATCC-3′ (SEQ ID NO: 936)5′-UUUUUGCCCUGCGUGACCAGAUCCC-3′ (SEQ ID NO: 1264)3′-GAAAAAACGGGACGCACUGGUCUAGGG-5′ (SEQ ID NO: 610) MYC-1715 Target:5′-CTTTTTTGCCCTGCGTGACCAGATCCC-3′ (SEQ ID NO: 937)5′-UUUUGCCCUGCGUGACCAGAUCCCG-3′ (SEQ ID NO: 1265)3′-AAAAAACGGGACGCACUGGUCUAGGGC-5′ (SEQ ID NO: 611) MYC-1716 Target:5′-TTTTTTGCCCTGCGTGACCAGATCCCG-3′ (SEQ ID NO: 938)5′-UUUGCCCUGCGUGACCAGAUCCCGG-3′ (SEQ ID NO: 1266)3′-AAAAACGGGACGCACUGGUCUAGGGCC-5′ (SEQ ID NO: 612) MYC-1717 Target:5′-TTTTTGCCCTGCGTGACCAGATCCCGG-3′ (SEQ ID NO: 939)5′-UUGCCCUGCGUGACCAGAUCCCGGA-3′ (SEQ ID NO: 1267)3′-AAAACGGGACGCACUGGUCUAGGGCCU-5′ (SEQ ID NO: 613) MYC-1718 Target:5′-TTTTGCCCTGCGTGACCAGATCCCGGA-3′ (SEQ ID NO: 940)5′-UGCCCUGCGUGACCAGAUCCCGGAG-3′ (SEQ ID NO: 1268)3′-AAACGGGACGCACUGGUCUAGGGCCUC-5′ (SEQ ID NO: 614) MYC-1719 Target:5′-TTTGCCCTGCGTGACCAGATCCCGGAG-3′ (SEQ ID NO: 941)5′-GCCCUGCGUGACCAGAUCCCGGAGU-3′ (SEQ ID NO: 1269)3′-AACGGGACGCACUGGUCUAGGGCCUCA-5′ (SEQ ID NO: 615) MYC-1720 Target:5′-TTGCCCTGCGTGACCAGATCCCGGAGT-3′ (SEQ ID NO: 942)5′-CCCUGCGUGACCAGAUCCCGGAGUU-3′ (SEQ ID NO: 1270)3′-ACGGGACGCACUGGUCUAGGGCCUCAA-5′ (SEQ ID NO: 616) MYC-1721 Target:5′-TGCCCTGCGTGACCAGATCCCGGAGTT-3′ (SEQ ID NO: 943)5′-GGAAACGACGAGAACAGUUGAAACA-3′ (SEQ ID NO: 1271)3′-CGCCUUUGCUGCUCUUGUCAACUUUGU-5′ (SEQ ID NO: 617) MYC-1856 Target:5′-GCGGAAACGACGAGAACAGTTGAAACA-3′ (SEQ ID NO: 944)5′-GAAACGACGAGAACAGUUGAAACAC-3′ (SEQ ID NO: 1272)3′-GCCUUUGCUGCUCUUGUCAACUUUGUG-5′ (SEQ ID NO: 618) MYC-1857 Target:5′-CGGAAACGACGAGAACAGTTGAAACAC-3′ (SEQ ID NO: 945)5′-UUUAACAGAUUUGUAUUUAAGAAUU-3′ (SEQ ID NO: 1273)3′-AGAAAUUGUCUAAACAUAAAUUCUUAA-5′ (SEQ ID NO: 619) MYC-2115 Target:5′-TCTTTAACAGATTTGTATTTAAGAATT-3′ (SEQ ID NO: 946)5′-UUAACAGAUUUGUAUUUAAGAAUUG-3′ (SEQ ID NO: 1274)3′-GAAAUUGUCUAAACAUAAAUUCUUAAC-5′ (SEQ ID NO: 620) MYC-2116 Target:5′-CTTTAACAGATTTGTATTTAAGAATTG-3′ (SEQ ID NO: 947)5′-AAAUGUAAAUAACUUUAAUAAAACG-3′ (SEQ ID NO: 1275)3′-AAUUUACAUUUAUUGAAAUUAUUUUGC-5′ (SEQ ID NO: 621) MYC-2193 Target:5′-TTAAATGTAAATAACTTTAATAAAACG-3′ (SEQ ID NO: 948)5′-AAUGUAAAUAACUUUAAUAAAACGU-3′ (SEQ ID NO: 1276)3′-AUUUACAUUUAUUGAAAUUAUUUUGCA-5′ (SEQ ID NO: 622) MYC-2194 Target:5′-TAAATGTAAATAACTTTAATAAAACGT-3′ (SEQ ID NO: 949)5′-AUGUAAAUAACUUUAAUAAAACGUU-3′ (SEQ ID NO: 1277)3′-UUUACAUUUAUUGAAAUUAUUUUGCAA-5′ (SEQ ID NO: 623) MYC-2195 Target:5′-AAATGTAAATAACTTTAATAAAACGTT-3′ (SEQ ID NO: 950)5′-UGUAAAUAACUUUAAUAAAACGUUU-3′ (SEQ ID NO: 1278)3′-UUACAUUUAUUGAAAUUAUUUUGCAAA-5′ (SEQ ID NO: 624) MYC-2196 Target:5′-AATGTAAATAACTTTAATAAAACGTTT-3′ (SEQ ID NO: 951)5′-GUAAAUAACUUUAAUAAAACGUUUA-3′ (SEQ ID NO: 1279)3′-UACAUUUAUUGAAAUUAUUUUGCAAAU-5′ (SEQ ID NO: 625) MYC-2197 Target:5′-ATGTAAATAACTTTAATAAAACGTTTA-3′ (SEQ ID NO: 952)5′-UAAAUAACUUUAAUAAAACGUUUAU-3′ (SEQ ID NO: 1280)3′-ACAUUUAUUGAAAUUAUUUUGCAAAUA-5′ (SEQ ID NO: 626) MYC-2198 Target:5′-TGTAAATAACTTTAATAAAACGTTTAT-3′ (SEQ ID NO: 953)5′-AAAUAACUUUAAUAAAACGUUUAUA-3′ (SEQ ID NO: 1281)3′-CAUUUAUUGAAAUUAUUUUGCAAAUAU-5′ (SEQ ID NO: 627) MYC-2199 Target:5′-GTAAATAACTTTAATAAAACGTTTATA-3′ (SEQ ID NO: 954)5′-AAUAACUUUAAUAAAACGUUUAUAG-3′ (SEQ ID NO: 1282)3′-AUUUAUUGAAAUUAUUUUGCAAAUAUC-5′ (SEQ ID NO: 628) MYC-2200 Target:5′-TAAATAACTTTAATAAAACGTTTATAG-3′ (SEQ ID NO: 955)5′-AUAACUUUAAUAAAACGUUUAUAGC-3′ (SEQ ID NO: 1283)3′-UUUAUUGAAAUUAUUUUGCAAAUAUCG-5′ (SEQ ID NO: 629) MYC-2201 Target:5′-AAATAACTTTAATAAAACGTTTATAGC-3′ (SEQ ID NO: 956)5′-UAACUUUAAUAAAACGUUUAUAGCA-3′ (SEQ ID NO: 1284)3′-UUAUUGAAAUUAUUUUGCAAAUAUCGU-5′ (SEQ ID NO: 630) MYC-2202 Target:5′-AATAACTTTAATAAAACGTTTATAGCA-3′ (SEQ ID NO: 957)5′-AACUUUAAUAAAACGUUUAUAGCAG-3′ (SEQ ID NO: 1285)3′-UAUUGAAAUUAUUUUGCAAAUAUCGUC-5′ (SEQ ID NO: 631) MYC-2203 Target:5′-ATAACTTTAATAAAACGTTTATAGCAG-3′ (SEQ ID NO: 958)5′-ACUUUAAUAAAACGUUUAUAGCAGU-3′ (SEQ ID NO: 1286)3′-AUUGAAAUUAUUUUGCAAAUAUCGUCA-5′ (SEQ ID NO: 632) MYC-2204 Target:5′-TAACTTTAATAAAACGTTTATAGCAGT-3′ (SEQ ID NO: 959)5′-CUUUAAUAAAACGUUUAUAGCAGUU-3′ (SEQ ID NO: 1287)3′-UUGAAAUUAUUUUGCAAAUAUCGUCAA-5′ (SEQ ID NO: 633) MYC-2205 Target:5′-AACTTTAATAAAACGTTTATAGCAGTT-3′ (SEQ ID NO: 960)5′-UUUUUAAAGUUGAUUUUUUUCUAUU-3′ (SEQ ID NO: 1288)3′-CGAAAAAUUUCAACUAAAAAAAGAUAA-5′ (SEQ ID NO: 634) MYC-2313 Target:5′-GCTTTTTAAAGTTGATTTTTTTCTATT-3′ (SEQ ID NO: 961)5′-UUUUAAAGUUGAUUUUUUUCUAUUG-3′ (SEQ ID NO: 1289)3′-GAAAAAUUUCAACUAAAAAAAGAUAAC-5′ (SEQ ID NO: 635) MYC-2314 Target:5′-CTTTTTAAAGTTGATTTTTTTCTATTG-3′ (SEQ ID NO: 962)5′-UUUAAAGUUGAUUUUUUUCUAUUGU-3′ (SEQ ID NO: 1290)3′-AAAAAUUUCAACUAAAAAAAGAUAACA-5′ (SEQ ID NO: 636) MYC-2315 Target:5′-TTTTTAAAGTTGATTTTTTTCTATTGT-3′ (SEQ ID NO: 963)5′-UUAAAGUUGAUUUUUUUCUAUUGUU-3′ (SEQ ID NO: 1291)3′-AAAAUUUCAACUAAAAAAAGAUAACAA-5′ (SEQ ID NO: 637) MYC-2316 Target:5′-TTTTAAAGTTGATTTTTTTCTATTGTT-3′ (SEQ ID NO: 964)5′-UAAAGUUGAUUUUUUUCUAUUGUUU-3′ (SEQ ID NO: 1292)3′-AAAUUUCAACUAAAAAAAGAUAACAAA-5′ (SEQ ID NO: 638) MYC-2317 Target:5′-TTTAAAGTTGATTTTTTTCTATTGTTT-3′ (SEQ ID NO: 965)5′-AAAGUUGAUUUUUUUCUAUUGUUUU-3′ (SEQ ID NO: 1293)3′-AAUUUCAACUAAAAAAAGAUAACAAAA-5′ (SEQ ID NO: 639) MYC-2318 Target:5′-TTAAAGTTGATTTTTTTCTATTGTTTT-3′ (SEQ ID NO: 966)5′-AAGUUGAUUUUUUUCUAUUGUUUUU-3′ (SEQ ID NO: 1294)3′-AUUUCAACUAAAAAAAGAUAACAAAAA-5′ (SEQ ID NO: 640) MYC-2319 Target:5′-TAAAGTTGATTTTTTTCTATTGTTTTT-3′ (SEQ ID NO: 967)5′-AGUUGAUUUUUUUCUAUUGUUUUUA-3′ (SEQ ID NO: 1295)3′-UUUCAACUAAAAAAAGAUAACAAAAAU-5′ (SEQ ID NO: 641) MYC-2320 Target:5′-AAAGTTGATTTTTTTCTATTGTTTTTA-3′ (SEQ ID NO: 968)5′-GUUGAUUUUUUUCUAUUGUUUUUAG-3′ (SEQ ID NO: 1296)3′-UUCAACUAAAAAAAGAUAACAAAAAUC-5′ (SEQ ID NO: 642) MYC-2321 Target:5′-AAGTTGATTTTTTTCTATTGTTTTTAG-3′ (SEQ ID NO: 969)5′-UUGAUUUUUUUCUAUUGUUUUUAGA-3′ (SEQ ID NO: 1297)3′-UCAACUAAAAAAAGAUAACAAAAAUCU-5′ (SEQ ID NO: 643) MYC-2322 Target:5′-AGTTGATTTTTTTCTATTGTTTTTAGA-3′ (SEQ ID NO: 970)5′-UGAUUUUUUUCUAUUGUUUUUAGAA-3′ (SEQ ID NO: 1298)3′-CAACUAAAAAAAGAUAACAAAAAUCUU-5′ (SEQ ID NO: 644) MYC-2323 Target:5′-GTTGATTTTTTTCTATTGTTTTTAGAA-3′ (SEQ ID NO: 971)5′-GAUUUUUUUCUAUUGUUUUUAGAAA-3′ (SEQ ID NO: 1299)3′-AACUAAAAAAAGAUAACAAAAAUCUUU-5′ (SEQ ID NO: 645) MYC-2324 Target:5′-TTGATTTTTTTCTATTGTTTTTAGAAA-3′ (SEQ ID NO: 972)5′-AUUUUUUUCUAUUGUUUUUAGAAAA-3′ (SEQ ID NO: 1300)3′-ACUAAAAAAAGAUAACAAAAAUCUUUU-5′ (SEQ ID NO: 646) MYC-2325 Target:5′-TGATTTTTTTCTATTGTTTTTAGAAAA-3′ (SEQ ID NO: 973)5′-UUUUUUUCUAUUGUUUUUAGAAAAA-3′ (SEQ ID NO: 1301)3′-CUAAAAAAAGAUAACAAAAAUCUUUUU-5′ (SEQ ID NO: 647) MYC-2326 Target:5′-GATTTTTTTCTATTGTTTTTAGAAAAA-3′ (SEQ ID NO: 974)5′-UUUUUUCUAUUGUUUUUAGAAAAAA-3′ (SEQ ID NO: 1302)3′-UAAAAAAAGAUAACAAAAAUCUUUUUU-5′ (SEQ ID NO: 648) MYC-2327 Target:5′-ATTTTTTTCTATTGTTTTTAGAAAAAA-3′ (SEQ ID NO: 975)5′-UUUUUCUAUUGUUUUUAGAAAAAAU-3′ (SEQ ID NO: 1303)3′-AAAAAAAGAUAACAAAAAUCUUUUUUA-5′ (SEQ ID NO: 649) MYC-2328 Target:5′-TTTTTTTCTATTGTTTTTAGAAAAAAT-3′ (SEQ ID NO: 976)5′-UUUUCUAUUGUUUUUAGAAAAAAUA-3′ (SEQ ID NO: 1304)3′-AAAAAAGAUAACAAAAAUCUUUUUUAU-5′ (SEQ ID NO: 650) MYC-2329 Target:5′-TTTTTTCTATTGTTTTTAGAAAAAATA-3′ (SEQ ID NO: 977)5′-UUUCUAUUGUUUUUAGAAAAAAUAA-3′ (SEQ ID NO: 1305)3′-AAAAAGAUAACAAAAAUCUUUUUUAUU-5′ (SEQ ID NO: 651) MYC-2330 Target:5′-TTTTTCTATTGTTTTTAGAAAAAATAA-3′ (SEQ ID NO: 978)5′-UUCUAUUGUUUUUAGAAAAAAUAAA-3′ (SEQ ID NO: 1306)3′-AAAAGAUAACAAAAAUCUUUUUUAUUU-5′ (SEQ ID NO: 652) MYC-2331 Target:5′-TTTTCTATTGTTTTTAGAAAAAATAAA-3′ (SEQ ID NO: 979)5′-UCUAUUGUUUUUAGAAAAAAUAAAA-3′ (SEQ ID NO: 1307)3′-AAAGAUAACAAAAAUCUUUUUUAUUUU-5′ (SEQ ID NO: 653) MYC-2332 Target:5′-TTTCTATTGTTTTTAGAAAAAATAAAA-3′ (SEQ ID NO: 980)5′-CUAUUGUUUUUAGAAAAAAUAAAAU-3′ (SEQ ID NO: 1308)3′-AAGAUAACAAAAAUCUUUUUUAUUUUA-5′ (SEQ ID NO: 654) MYC-2333 Target:5′-TTCTATTGTTTTTAGAAAAAATAAAAT-3′ (SEQ ID NO: 981)

TABLE 4 Selected Mouse Anti-MYC DsiRNAs (Asymmetrics)5′-GGAUCCUGAGUCGCAGUAUAAAAga-3′ (SEQ ID NO: 3271)3′-UCCCUAGGACUCAGCGUCAUAUUUUCU-5′ (SEQ ID NO: 3415) MYC-m187 Target:5′-AGGGATCCTGAGTCGCAGTATAAAAGA-3′ (SEQ ID NO: 3559)5′-GAGUCGCAGUAUAAAAGAAGCUUtt-3′ (SEQ ID NO: 3272)3′-GACUCAGCGUCAUAUUUUCUUCGAAAA-5′ (SEQ ID NO: 3416) MYC-m194 Target:5′-CTGAGTCGCAGTATAAAAGAAGCTTTT-3′ (SEQ ID NO: 3560)5′-GCAGUAUAAAAGAAGCUUUUCGGgc-3′ (SEQ ID NO: 3273)3′-AGCGUCAUAUUUUCUUCGAAAAGCCCG-5′ (SEQ ID NO: 3417) MYC-m199 Target:5′-TCGCAGTATAAAAGAAGCTTTTCGGGC-3′ (SEQ ID NO: 3561)5′-GAAGCUUUUCGGGCGUUUUUUUCtg-3′ (SEQ ID NO: 3274)3′-UUCUUCGAAAAGCCCGCAAAAAAAGAC-5′ (SEQ ID NO: 3418) MYC-m210 Target:5′-AAGAAGCTTTTCGGGCGTTTTTTTCTG-3′ (SEQ ID NO: 3562)5′-CGUUUUUUUCUGACUCGCUGUAGta-3′ (SEQ ID NO: 3275)3′-CCGCAAAAAAAGACUGAGCGACAUCAU-5′ (SEQ ID NO: 3419) MYC-m223 Target:5′-GGCGTTTTTTTCTGACTCGCTGTAGTA-3′ (SEQ ID NO: 3563)5′-AGGGAGUGAGCGGACGGUUGGAAga-3′ (SEQ ID NO: 3276)3′-UCUCCCUCACUCGCCUGCCAACCUUCU-5′ (SEQ ID NO: 3420) MYC-m265 Target:5′-AGAGGGAGTGAGCGGACGGTTGGAAGA-3′ (SEQ ID NO: 3564)5′-AGCGGACGGUUGGAAGAGCCGUGtg-3′ (SEQ ID NO: 3277)3′-ACUCGCCUGCCAACCUUCUCGGCACAC-5′ (SEQ ID NO: 3421) MYC-m273 Target:5′-TGAGCGGACGGTTGGAAGAGCCGTGTG-3′ (SEQ ID NO: 3565)5′-CCUAAGAAGGCAGCUCUGGAGUGag-3′ (SEQ ID NO: 3278)3′-CUGGAUUCUUCCGUCGAGACCUCACUC-5′ (SEQ ID NO: 3422) MYC-m321 Target:5′-GACCTAAGAAGGCAGCTCTGGAGTGAG-3′ (SEQ ID NO: 3566)5′-ACCCUGCGACUGACCCAACAUCAgc-3′ (SEQ ID NO: 3279)3′-GUUGGGACGCUGACUGGGUUGUAGUCG-5′ (SEQ ID NO: 3423) MYC-m384 Target:5′-CAACCCTGCGACTGACCCAACATCAGC-3′ (SEQ ID NO: 3567)5′-GCAGACACUUCUCACUGGAACUUac-3′ (SEQ ID NO: 3280)3′-CCCGUCUGUGAAGAGUGACCUUGAAUG-5′ (SEQ ID NO: 3424) MYC-m455 Target:5′-GGGCAGACACTTCTCACTGGAACTTAC-3′ (SEQ ID NO: 3568)5′-CACUUCUCACUGGAACUUACAAUct-3′ (SEQ ID NO: 3281)3′-CUGUGAAGAGUGACCUUGAAUGUUAGA-5′ (SEQ ID NO: 3425) MYC-m460 Target:5′-GACACTTCTCACTGGAACTTACAATCT-3′ (SEQ ID NO: 3569)5′-CUGGAACUUACAAUCUGCGAGCCag-3′ (SEQ ID NO: 3282)3′-GUGACCUUGAAUGUUAGACGCUCGGUC-5′ (SEQ ID NO: 3426) MYC-m469 Target:5′-CACTGGAACTTACAATCTGCGAGCCAG-3′ (SEQ ID NO: 3570)5′-ACAAUCUGCGAGCCAGGACAGGAct-3′ (SEQ ID NO: 3283)3′-AAUGUUAGACGCUCGGUCCUGUCCUGA-5′ (SEQ ID NO: 3427) MYC-m478 Target:5′-TTACAATCTGCGAGCCAGGACAGGACT-3′ (SEQ ID NO: 3571)5′-AAGAGCUCCUCGAGCUGUUUGAAgg-3′ (SEQ ID NO: 3284)3′-UUUUCUCGAGGAGCUCGACAAACUUCC-5′ (SEQ ID NO: 3428) MYC-m581 Target:5′-AAAAGAGCTCCTCGAGCTGTTTGAAGG-3′ (SEQ ID NO: 3572)5′-CGAGCUGUUUGAAGGCUGGAUUUcc-3′ (SEQ ID NO: 3285)3′-GAGCUCGACAAACUUCCGACCUAAAGG-5′ (SEQ ID NO: 3429) MYC-m591 Target:5′-CTCGAGCTGTTTGAAGGCTGGATTTCC-3′ (SEQ ID NO: 3573)5′-GUUUGAAGGCUGGAUUUCCUUUGgg-3′ (SEQ ID NO: 3286)3′-GACAAACUUCCGACCUAAAGGAAACCC-5′ (SEQ ID NO: 3430) MYC-m597 Target:5′-CTGTTTGAAGGCTGGATTTCCTTTGGG-3′ (SEQ ID NO: 3574)5′-GAUUUCCUUUGGGCGUUGGAAACcc-3′ (SEQ ID NO: 3287)3′-ACCUAAAGGAAACCCGCAACCUUUGGG-5′ (SEQ ID NO: 3431) MYC-m609 Target:5′-TGGATTTCCTTTGGGCGTTGGAAACCC-3′ (SEQ ID NO: 3575)5′-CUCAACGUGAACUUCACCAACAGga-3′ (SEQ ID NO: 3288)3′-GGGAGUUGCACUUGAAGUGGUUGUCCU-5′ (SEQ ID NO: 3432) MYC-m657 Target:5′-CCCTCAACGTGAACTTCACCAACAGGA-3′ (SEQ ID NO: 3576)5′-GUGAACUUCACCAACAGGAACUAtg-3′ (SEQ ID NO: 3289)3′-UGCACUUGAAGUGGUUGUCCUUGAUAC-5′ (SEQ ID NO: 3433) MYC-m663 Target:5′-ACGTGAACTTCACCAACAGGAACTATG-3′ (SEQ ID NO: 3577)5′-GACUCCGUACAGCCCUAUUUCAUct-3′ (SEQ ID NO: 3290)3′-UGCUGAGGCAUGUCGGGAUAAAGUAGA-5′ (SEQ ID NO: 3434) MYC-m699 Target:5′-ACGACTCCGTACAGCCCTATTTCATCT-3′ (SEQ ID NO: 3578)5′-GCGACGAGGAAGAGAAUUUCUAUca-3′ (SEQ ID NO: 3291)3′-GACGCUGCUCCUUCUCUUAAAGAUAGU-5′ (SEQ ID NO: 3435) MYC-m724 Target:5′-CTGCGACGAGGAAGAGAATTTCTATCA-3′ (SEQ ID NO: 3579)5′-GAAGAGAAUUUCUAUCACCAGCAac-3′ (SEQ ID NO: 3292)3′-UCCUUCUCUUAAAGAUAGUGGUCGUUG-5′ (SEQ ID NO: 3436) MYC-m732 Target:5′-AGGAAGAGAATTTCTATCACCAGCAAC-3′ (SEQ ID NO: 3580)5′-GUGAGGAUAUCUGGAAGAAAUUCga-3′ (SEQ ID NO: 3293)3′-GUCACUCCUAUAGACCUUCUUUAAGCU-5′ (SEQ ID NO: 3437) MYC-m787 Target:5′-CAGTGAGGATATCTGGAAGAAATTCGA-3′ (SEQ ID NO: 3581)5′-GAAGAAAUUCGAGCUGCUUCCCAcc-3′ (SEQ ID NO: 3294)3′-ACCUUCUUUAAGCUCGACGAAGGGUGG-5′ (SEQ ID NO: 3438) MYC-m800 Target:5′-TGGAAGAAATTCGAGCTGCTTCCCACC-3′ (SEQ ID NO: 3582)5′-GGGCUCUGCUCUCCAUCCUAUGUtg-3′ (SEQ ID NO: 3295)3′-GGCCCGAGACGAGAGGUAGGAUACAAC-5′ (SEQ ID NO: 3439) MYC-m852 Target:5′-CCGGGCTCTGCTCTCCATCCTATGTTG-3′ (SEQ ID NO: 3583)5′-CUGCUCUCCAUCCUAUGUUGCGGtc-3′ (SEQ ID NO: 3296)3′-GAGACGAGAGGUAGGAUACAACGCCAG-5′ (SEQ ID NO: 3440) MYC-m857 Target:5′-CTCTGCTCTCCATCCTATGTTGCGGTC-3′ (SEQ ID NO: 3584)5′-UCCUAUGUUGCGGUCGCUACGUCct-3′ (SEQ ID NO: 3297)3′-GUAGGAUACAACGCCAGCGAUGCAGGA-5′ (SEQ ID NO: 3441) MYC-m867 Target:5′-CATCCTATGTTGCGGTCGCTACGTCCT-3′ (SEQ ID NO: 3585)5′-GUUGCGGUCGCUACGUCCUUCUCcc-3′ (SEQ ID NO: 3298)3′-UACAACGCCAGCGAUGCAGGAAGAGGG-5′ (SEQ ID NO: 3442) MYC-m873 Target:5′-ATGTTGCGGTCGCTACGTCCTTCTCCC-3′ (SEQ ID NO: 3586)5′-CCGAUCAGCUGGAGAUGAUGACCga-3′ (SEQ ID NO: 3299)3′-GCGGCUAGUCGACCUCUACUACUGGCU-5′ (SEQ ID NO: 3443) MYC-m940 Target:5′-CGCCGATCAGCTGGAGATGATGACCGA-3′ (SEQ ID NO: 3587)5′-CUGGAGAUGAUGACCGAGUUACUtg-3′ (SEQ ID NO: 3300)3′-UCGACCUCUACUACUGGCUCAAUGAAC-5′ (SEQ ID NO: 3444) MYC-m948 Target:5′-AGCTGGAGATGATGACCGAGTTACTTG-3′ (SEQ ID NO: 3588)5′-GAUGACCGAGUUACUUGGAGGAGac-3′ (SEQ ID NO: 3301)3′-UACUACUGGCUCAAUGAACCUCCUCUG-5′ (SEQ ID NO: 3445) MYC-m956 Target:5′-ATGATGACCGAGTTACTTGGAGGAGAC-3′ (SEQ ID NO: 3589)5′-AGUUACUUGGAGGAGACAUGGUGaa-3′ (SEQ ID NO: 3302)3′-GCUCAAUGAACCUCCUCUGUACCACUU-5′ (SEQ ID NO: 3446) MYC-m964 Target:5′-CGAGTTACTTGGAGGAGACATGGTGAA-3′ (SEQ ID NO: 3590)5′-CUUGGAGGAGACAUGGUGAACCAga-3′ (SEQ ID NO: 3303)3′-AUGAACCUCCUCUGUACCACUUGGUCU-5′ (SEQ ID NO: 3447) MYC-m969 Target:5′-TACTTGGAGGAGACATGGTGAACCAGA-3′ (SEQ ID NO: 3591)5′-CAUGGUGAACCAGAGCUUCAUCUgc-3′ (SEQ ID NO: 3304)3′-CUGUACCACUUGGUCUCGAAGUAGACG-5′ (SEQ ID NO: 3448) MYC-m980 Target:5′-GACATGGTGAACCAGAGCTTCATCTGC-3′ (SEQ ID NO: 3592)5′-CCAGAGCUUCAUCUGCGAUCCUGac-3′ (SEQ ID NO: 3305)3′-UUGGUCUCGAAGUAGACGCUAGGACUG-5′ (SEQ ID NO: 3449) MYC-m989 Target:5′-AACCAGAGCTTCATCTGCGATCCTGAC-3′ (SEQ ID NO: 3593)5′-GCUUCAUCUGCGAUCCUGACGACga-3′ (SEQ ID NO: 3306)3′-CUCGAAGUAGACGCUAGGACUGCUGCU-5′ (SEQ ID NO: 3450) MYC-m994 Target:5′-GAGCTTCATCTGCGATCCTGACGACGA-3′ (SEQ ID NO: 3594)5′-UCUGCGAUCCUGACGACGAGACCtt-3′ (SEQ ID NO: 3307)3′-GUAGACGCUAGGACUGCUGCUCUGGAA-5′ (SEQ ID NO: 3451) MYC-m1000 Target:5′-CATCTGCGATCCTGACGACGAGACCTT-3′ (SEQ ID NO: 3595)5′-AUCCUGACGACGAGACCUUCAUCaa-3′ (SEQ ID NO: 3308)3′-GCUAGGACUGCUGCUCUGGAAGUAGUU-5′ (SEQ ID NO: 3452) MYC-m1006 Target:5′-CGATCCTGACGACGAGACCTTCATCAA-3′ (SEQ ID NO: 3596)5′-GACGAGACCUUCAUCAAGAACAUca-3′ (SEQ ID NO: 3309)3′-UGCUGCUCUGGAAGUAGUUCUUGUAGU-5′ (SEQ ID NO: 3453) MYC-m1014 Target:5′-ACGACGAGACCTTCATCAAGAACATCA-3′ (SEQ ID NO: 3597)5′-ACCUUCAUCAAGAACAUCAUCAUcc-3′ (SEQ ID NO: 3310)3′-UCUGGAAGUAGUUCUUGUAGUAGUAGG-5′ (SEQ ID NO: 3454) MYC-m1020 Target:5′-AGACCTTCATCAAGAACATCATCATCC-3′ (SEQ ID NO: 3598)5′-AAGAACAUCAUCAUCCAGGACUGta-3′ (SEQ ID NO: 3311)3′-AGUUCUUGUAGUAGUAGGUCCUGACAU-5′ (SEQ ID NO: 3455) MYC-m1029 Target:5′-TCAAGAACATCATCATCCAGGACTGTA-3′ (SEQ ID NO: 3599)5′-GGACUGUAUGUGGAGCGGUUUCUca-3′ (SEQ ID NO: 3312)3′-GUCCUGACAUACACCUCGCCAAAGAGU-5′ (SEQ ID NO: 3456) MYC-m1046 Target:5′-CAGGACTGTATGTGGAGCGGTTTCTCA-3′ (SEQ ID NO: 3600)5′-UGCUCCACCUCCAGCCUGUACCUgc-3′ (SEQ ID NO: 3313)3′-AGACGAGGUGGAGGUCGGACAUGGACG-5′ (SEQ ID NO: 3457) MYC-m1164 Target:5′-TCTGCTCCACCTCCAGCCTGTACCTGC-3′ (SEQ ID NO: 3601)5′-ACCUCCAGCCUGUACCUGCAGGAcc-3′ (SEQ ID NO: 3314)3′-GGUGGAGGUCGGACAUGGACGUCCUGG-5′ (SEQ ID NO: 3458) MYC-m1170 Target:5′-CCACCTCCAGCCTGTACCTGCAGGACC-3′ (SEQ ID NO: 3602)5′-AGCCUGUACCUGCAGGACCUCACcg-3′ (SEQ ID NO: 3315)3′-GGUCGGACAUGGACGUCCUGGAGUGGC-5′ (SEQ ID NO: 3459) MYC-m1176 Target:5′-CCAGCCTGTACCTGCAGGACCTCACCG-3′ (SEQ ID NO: 3603)5′-GCAGCUCGCCCAAAUCCUGUACCtc-3′ (SEQ ID NO: 3316)3′-GUCGUCGAGCGGGUUUAGGACAUGGAG-5′ (SEQ ID NO: 3460) MYC-m1258 Target:5′-CAGCAGCTCGCCCAAATCCTGTACCTC-3′ (SEQ ID NO: 3604)5′-AAAUCCUGUACCUCGUCCGAUUCca-3′ (SEQ ID NO: 3317)3′-GGUUUAGGACAUGGAGCAGGCUAAGGU-5′ (SEQ ID NO: 3461) MYC-m1269 Target:5′-CCAAATCCTGTACCTCGTCCGATTCCA-3′ (SEQ ID NO: 3605)5′-CACCAGCAGCGACUCUGAAGAAGag-3′ (SEQ ID NO: 3318)3′-UGGUGGUCGUCGCUGAGACUUCUUCUC-5′ (SEQ ID NO: 3462) MYC-m1391 Target:5′-ACCACCAGCAGCGACTCTGAAGAAGAG-3′ (SEQ ID NO: 3606)5′-GCAGCGACUCUGAAGAAGAGCAAga-3′ (SEQ ID NO: 3319)3′-GUCGUCGCUGAGACUUCUUCUCGUUCU-5′ (SEQ ID NO: 3463) MYC-m1396 Target:5′-CAGCAGCGACTCTGAAGAAGAGCAAGA-3′ (SEQ ID NO: 3607)5′-ACUCUGAAGAAGAGCAAGAAGAUga-3′ (SEQ ID NO: 3320)3′-GCUGAGACUUCUUCUCGUUCUUCUACU-5′ (SEQ ID NO: 3464) MYC-m1402 Target:5′-CGACTCTGAAGAAGAGCAAGAAGATGA-3′ (SEQ ID NO: 3608)5′-GAAGAAGAGCAAGAAGAUGAGGAag-3′ (SEQ ID NO: 3321)3′-GACUUCUUCUCGUUCUUCUACUCCUUC-5′ (SEQ ID NO: 3465) MYC-m1407 Target:5′-CTGAAGAAGAGCAAGAAGATGAGGAAG-3′ (SEQ ID NO: 3609)5′-AGCAAGAAGAUGAGGAAGAAAUUga-3′ (SEQ ID NO: 3322)3′-UCUCGUUCUUCUACUCCUUCUUUAACU-5′ (SEQ ID NO: 3466) MYC-m1414 Target:5′-AGAGCAAGAAGATGAGGAAGAAATTGA-3′ (SEQ ID NO: 3610)5′-AAGAUGAGGAAGAAAUUGAUGUGgt-3′ (SEQ ID NO: 3323)3′-UCUUCUACUCCUUCUUUAACUACACCA-5′ (SEQ ID NO: 3467) MYC-m1420 Target:5′-AGAAGATGAGGAAGAAATTGATGTGGT-3′ (SEQ ID NO: 3611)5′-AGGAAGAAAUUGAUGUGGUGUCUgt-3′ (SEQ ID NO: 3324)3′-ACUCCUUCUUUAACUACACCACAGACA-5′ (SEQ ID NO: 3468) MYC-m1426 Target:5′-TGAGGAAGAAATTGATGTGGTGTCTGT-3′ (SEQ ID NO: 3612)5′-GAAAUUGAUGUGGUGUCUGUGGAga-3′ (SEQ ID NO: 3325)3′-UUCUUUAACUACACCACAGACACCUCU-5′ (SEQ ID NO: 3469) MYC-m1431 Target:5′-AAGAAATTGATGTGGTGTCTGTGGAGA-3′ (SEQ ID NO: 3613)5′-GAUGUGGUGUCUGUGGAGAAGAGgc-3′ (SEQ ID NO: 3326)3′-AACUACACCACAGACACCUCUUCUCCG-5′ (SEQ ID NO: 3470) MYC-m1437 Target:5′-TTGATGTGGTGTCTGTGGAGAAGAGGC-3′ (SEQ ID NO: 3614)5′-GUGUCUGUGGAGAAGAGGCAAACcc-3′ (SEQ ID NO: 3327)3′-ACCACAGACACCUCUUCUCCGUUUGGG-5′ (SEQ ID NO: 3471) MYC-m1443 Target:5′-TGGTGTCTGTGGAGAAGAGGCAAACCC-3′ (SEQ ID NO: 3615)5′-GCCAAGAGGUCGGAGUCGGGCUCat-3′ (SEQ ID NO: 3328)3′-GACGGUUCUCCAGCCUCAGCCCGAGUA-5′ (SEQ ID NO: 3472) MYC-m1470 Target:5′-CTGCCAAGAGGTCGGAGTCGGGCTCAT-3′ (SEQ ID NO: 3616)5′-CAAGAGGUGCCACGUCUCCACUCac-3′ (SEQ ID NO: 3329)3′-GAGUUCUCCACGGUGCAGAGGUGAGUG-5′ (SEQ ID NO: 3473) MYC-m1541 Target:5′-CTCAAGAGGTGCCACGTCTCCACTCAC-3′ (SEQ ID NO: 3617)5′-GUCUCCACUCACCAGCACAACUAcg-3′ (SEQ ID NO: 3330)3′-UGCAGAGGUGAGUGGUCGUGUUGAUGC-5′ (SEQ ID NO: 3474) MYC-m1554 Target:5′-ACGTCTCCACTCACCAGCACAACTACG-3′ (SEQ ID NO: 3618)5′-GCCAAGAGGGCCAAGUUGGACAGtg-3′ (SEQ ID NO: 3331)3′-GACGGUUCUCCCGGUUCAACCUGUCAC-5′ (SEQ ID NO: 3475) MYC-m1614 Target:5′-CTGCCAAGAGGGCCAAGTTGGACAGTG-3′ (SEQ ID NO: 3619)5′-GAGGGCCAAGUUGGACAGUGGCAgg-3′ (SEQ ID NO: 3332)3′-UUCUCCCGGUUCAACCUGUCACCGUCC-5′ (SEQ ID NO: 3476) MYC-m1619 Target:5′-AAGAGGGCCAAGTTGGACAGTGGCAGG-3′ (SEQ ID NO: 3620)5′-AGUUGGACAGUGGCAGGGUCCUGaa-3′ (SEQ ID NO: 3333)3′-GUUCAACCUGUCACCGUCCCAGGACUU-5′ (SEQ ID NO: 3477) MYC-m1627 Target:5′-CAAGTTGGACAGTGGCAGGGTCCTGAA-3′ (SEQ ID NO: 3621)5′-GACAGUGGCAGGGUCCUGAAGCAga-3′ (SEQ ID NO: 3334)3′-ACCUGUCACCGUCCCAGGACUUCGUCU-5′ (SEQ ID NO: 3478) MYC-m1632 Target:5′-TGGACAGTGGCAGGGTCCTGAAGCAGA-3′ (SEQ ID NO: 3622)5′-GGCAGGGUCCUGAAGCAGAUCAGca-3′ (SEQ ID NO: 3335)3′-CACCGUCCCAGGACUUCGUCUAGUCGU-5′ (SEQ ID NO: 3479) MYC-m1638 Target:5′-GTGGCAGGGTCCTGAAGCAGATCAGCA-3′ (SEQ ID NO: 3623)5′-GUCCUGAAGCAGAUCAGCAACAAcc-3′ (SEQ ID NO: 3336)3′-CCCAGGACUUCGUCUAGUCGUUGUUGG-5′ (SEQ ID NO: 3480) MYC-m1644 Target:5′-GGGTCCTGAAGCAGATCAGCAACAACC-3′ (SEQ ID NO: 3624)5′-GAAGCAGAUCAGCAACAACCGCAag-3′ (SEQ ID NO: 3337)3′-GACUUCGUCUAGUCGUUGUUGGCGUUC-5′ (SEQ ID NO: 3481) MYC-m1649 Target:5′-CTGAAGCAGATCAGCAACAACCGCAAG-3′ (SEQ ID NO: 3625)5′-CGAGCUGAAGCGCAGCUUUUUUGcc-3′ (SEQ ID NO: 3338)3′-UUGCUCGACUUCGCGUCGAAAAAACGG-5′ (SEQ ID NO: 3482) MYC-m1754 Target:5′-AACGAGCTGAAGCGCAGCTTTTTTGCC-3′ (SEQ ID NO: 3626)5′-GCAGCUUUUUUGCCCUGCGUGACca-3′ (SEQ ID NO: 3339)3′-CGCGUCGAAAAAACGGGACGCACUGGU-5′ (SEQ ID NO: 3483) MYC-m1765 Target:5′-GCGCAGCTTTTTTGCCCTGCGTGACCA-3′ (SEQ ID NO: 3627)5′-CCUGCGUGACCAGAUCCCUGAAUtg-3′ (SEQ ID NO: 3340)3′-CGGGACGCACUGGUCUAGGGACUUAAC-5′ (SEQ ID NO: 3484) MYC-m1778 Target:5′-GCCCTGCGTGACCAGATCCCTGAATTG-3′ (SEQ ID NO: 3628)5′-ACCAGAUCCCUGAAUUGGAAAACaa-3′ (SEQ ID NO: 3341)3′-ACUGGUCUAGGGACUUAACCUUUUGUU-5′ (SEQ ID NO: 3485) MYC-m1786 Target:5′-TGACCAGATCCCTGAATTGGAAAACAA-3′ (SEQ ID NO: 3629)5′-CUGAAUUGGAAAACAACGAAAAGgc-3′ (SEQ ID NO: 3342)3′-GGGACUUAACCUUUUGUUGCUUUUCCG-5′ (SEQ ID NO: 3486) MYC-m1795 Target:5′-CCCTGAATTGGAAAACAACGAAAAGGC-3′ (SEQ ID NO: 3630)5′-AGGUAGUGAUCCUCAAAAAAGCCac-3′ (SEQ ID NO: 3343)3′-GUUCCAUCACUAGGAGUUUUUUCGGUG-5′ (SEQ ID NO: 3487) MYC-m1825 Target:5′-CAAGGTAGTGATCCTCAAAAAAGCCAC-3′ (SEQ ID NO: 3631)5′-CAAAAAAGCCACCGCCUACAUCCtg-3′ (SEQ ID NO: 3344)3′-GAGUUUUUUCGGUGGCGGAUGUAGGAC-5′ (SEQ ID NO: 3488) MYC-m1838 Target:5′-CTCAAAAAAGCCACCGCCTACATCCTG-3′ (SEQ ID NO: 3632)5′-GCCACCGCCUACAUCCUGUCCAUtc-3′ (SEQ ID NO: 3345)3′-UUCGGUGGCGGAUGUAGGACAGGUAAG-5′ (SEQ ID NO: 3489) MYC-m1845 Target:5′-AAGCCACCGCCTACATCCTGTCCATTC-3′ (SEQ ID NO: 3633)5′-CGCCUACAUCCUGUCCAUUCAAGca-3′ (SEQ ID NO: 3346)3′-UGGCGGAUGUAGGACAGGUAAGUUCGU-5′ (SEQ ID NO: 3490) MYC-m1850 Target:5′-ACCGCCTACATCCTGTCCATTCAAGCA-3′ (SEQ ID NO: 3634)5′-ACAUCCUGUCCAUUCAAGCAGACga-3′ (SEQ ID NO: 3347)3′-GAUGUAGGACAGGUAAGUUCGUCUGCU-5′ (SEQ ID NO: 3491) MYC-m1855 Target:5′-CTACATCCTGTCCATTCAAGCAGACGA-3′ (SEQ ID NO: 3635)5′-CUGUCCAUUCAAGCAGACGAGCAca-3′ (SEQ ID NO: 3348)3′-AGGACAGGUAAGUUCGUCUGCUCGUGU-5′ (SEQ ID NO: 3492) MYC-m1860 Target:5′-TCCTGTCCATTCAAGCAGACGAGCACA-3′ (SEQ ID NO: 3636)5′-CAGACGAGCACAAGCUCACCUCUga-3′ (SEQ ID NO: 3349)3′-UCGUCUGCUCGUGUUCGAGUGGAGACU-5′ (SEQ ID NO: 3493) MYC-m1873 Target:5′-AGCAGACGAGCACAAGCTCACCTCTGA-3′ (SEQ ID NO: 3637)5′-AGCACAAGCUCACCUCUGAAAAGga-3′ (SEQ ID NO: 3350)3′-GCUCGUGUUCGAGUGGAGACUUUUCCU-5′ (SEQ ID NO: 3494) MYC-m1879 Target:5′-CGAGCACAAGCTCACCTCTGAAAAGGA-3′ (SEQ ID NO: 3638)5′-CUCACCUCUGAAAAGGACUUAUUga-3′ (SEQ ID NO: 3351)3′-UCGAGUGGAGACUUUUCCUGAAUAACU-5′ (SEQ ID NO: 3495) MYC-m1887 Target:5′-AGCTCACCTCTGAAAAGGACTTATTGA-3′ (SEQ ID NO: 3639)5′-GAAAAGGACUUAUUGAGGAAACGac-3′ (SEQ ID NO: 3352)3′-GACUUUUCCUGAAUAACUCCUUUGCUG-5′ (SEQ ID NO: 3496) MYC-m1896 Target:5′-CTGAAAAGGACTTATTGAGGAAACGAC-3′ (SEQ ID NO: 3640)5′-GAGGAAACGACGAGAACAGUUGAaa-3′ (SEQ ID NO: 3353)3′-AACUCCUUUGCUGCUCUUGUCAACUUU-5′ (SEQ ID NO: 3497) MYC-m1910 Target:5′-TTGAGGAAACGACGAGAACAGTTGAAA-3′ (SEQ ID NO: 3641)5′-AAACUCGAACAGCUUCGAAACUCtg-3′ (SEQ ID NO: 3354)3′-UGUUUGAGCUUGUCGAAGCUUUGAGAC-5′ (SEQ ID NO: 3498) MYC-m1938 Target:5′-ACAAACTCGAACAGCTTCGAAACTCTG-3′ (SEQ ID NO: 3642)5′-CGAACAGCUUCGAAACUCUGGUGca-3′ (SEQ ID NO: 3355)3′-GAGCUUGUCGAAGCUUUGAGACCACGU-5′ (SEQ ID NO: 3499) MYC-m1943 Target:5′-CTCGAACAGCTTCGAAACTCTGGTGCA-3′ (SEQ ID NO: 3643)5′-UUCGAAACUCUGGUGCAUAAACUga-3′ (SEQ ID NO: 3356)3′-CGAAGCUUUGAGACCACGUAUUUGACU-5′ (SEQ ID NO: 3500) MYC-m1951 Target:5′-GCTTCGAAACTCTGGTGCATAAACTGA-3′ (SEQ ID NO: 3644)5′-ACUCUGGUGCAUAAACUGACCUAac-3′ (SEQ ID NO: 3357)3′-UUUGAGACCACGUAUUUGACUGGAUUG-5′ (SEQ ID NO: 3501) MYC-m1957 Target:5′-AAACTCTGGTGCATAAACTGACCTAAC-3′ (SEQ ID NO: 3645)5′-GUGCAUAAACUGACCUAACUCGAgg-3′ (SEQ ID NO: 3358)3′-ACCACGUAUUUGACUGGAUUGAGCUCC-5′ (SEQ ID NO: 3502) MYC-m1963 Target:5′-TGGTGCATAAACTGACCTAACTCGAGG-3′ (SEQ ID NO: 3646)5′-AGGAGGAGCUGGAAUCUCUCGUGag-3′ (SEQ ID NO: 3359)3′-GCUCCUCCUCGACCUUAGAGAGCACUC-5′ (SEQ ID NO: 3503) MYC-m1985 Target:5′-CGAGGAGGAGCTGGAATCTCTCGTGAG-3′ (SEQ ID NO: 3647)5′-GGAAUCUCUCGUGAGAGUAAGGAga-3′ (SEQ ID NO: 3360)3′-GACCUUAGAGAGCACUCUCAUUCCUCU-5′ (SEQ ID NO: 3504) MYC-m1995 Target:5′-CTGGAATCTCTCGTGAGAGTAAGGAGA-3′ (SEQ ID NO: 3648)5′-CUCGUGAGAGUAAGGAGAACGGUtc-3′ (SEQ ID NO: 3361)3′-GAGAGCACUCUCAUUCCUCUUGCCAAG-5′ (SEQ ID NO: 3505) MYC-m2002 Target:5′-CTCTCGTGAGAGTAAGGAGAACGGTTC-3′ (SEQ ID NO: 3649)5′-GUAAGGAGAACGGUUCCUUCUGAca-3′ (SEQ ID NO: 3362)3′-CUCAUUCCUCUUGCCAAGGAAGACUGU-5′ (SEQ ID NO: 3506) MYC-m2011 Target:5′-GAGTAAGGAGAACGGTTCCTTCTGACA-3′ (SEQ ID NO: 3650)5′-GAGAACGGUUCCUUCUGACAGAAct-3′ (SEQ ID NO: 3363)3′-UCCUCUUGCCAAGGAAGACUGUCUUGA-5′ (SEQ ID NO: 3507) MYC-m2016 Target:5′-AGGAGAACGGTTCCTTCTGACAGAACT-3′ (SEQ ID NO: 3651)5′-CGGUUCCUUCUGACAGAACUGAUgc-3′ (SEQ ID NO: 3364)3′-UUGCCAAGGAAGACUGUCUUGACUACG-5′ (SEQ ID NO: 3508) MYC-m2021 Target:5′-AACGGTTCCTTCTGACAGAACTGATGC-3′ (SEQ ID NO: 3652)5′-CAGAACUGAUGCGCUGGAAUUAAaa-3′ (SEQ ID NO: 3365)3′-CUGUCUUGACUACGCGACCUUAAUUUU-5′ (SEQ ID NO: 3509) MYC-m2034 Target:5′-GACAGAACTGATGCGCTGGAATTAAAA-3′ (SEQ ID NO: 3653)5′-CUGAUGCGCUGGAAUUAAAAUGCat-3′ (SEQ ID NO: 3366)3′-UUGACUACGCGACCUUAAUUUUACGUA-5′ (SEQ ID NO: 3510) MYC-m2039 Target:5′-AACTGATGCGCTGGAATTAAAATGCAT-3′ (SEQ ID NO: 3654)5′-GCGCUGGAAUUAAAAUGCAUGCUca-3′ (SEQ ID NO: 3367)3′-UACGCGACCUUAAUUUUACGUACGAGU-5′ (SEQ ID NO: 3511) MYC-m2044 Target:5′-ATGCGCTGGAATTAAAATGCATGCTCA-3′ (SEQ ID NO: 3655)5′-GGAAUUAAAAUGCAUGCUCAAAGcc-3′ (SEQ ID NO: 3368)3′-GACCUUAAUUUUACGUACGAGUUUCGG-5′ (SEQ ID NO: 3512) MYC-m2049 Target:5′-CTGGAATTAAAATGCATGCTCAAAGCC-3′ (SEQ ID NO: 3656)5′-AAAUGCAUGCUCAAAGCCUAACCtc-3′ (SEQ ID NO: 3369)3′-AUUUUACGUACGAGUUUCGGAUUGGAG-5′ (SEQ ID NO: 3513) MYC-m2056 Target:5′-TAAAATGCATGCTCAAAGCCTAACCTC-3′ (SEQ ID NO: 3657)5′-GCUCAAAGCCUAACCUCACAACCtt-3′ (SEQ ID NO: 3370)3′-UACGAGUUUCGGAUUGGAGUGUUGGAA-5′ (SEQ ID NO: 3514) MYC-m2064 Target:5′-ATGCTCAAAGCCTAACCTCACAACCTT-3′ (SEQ ID NO: 3658)5′-AAGCCUAACCUCACAACCUUGGCtg-3′ (SEQ ID NO: 3371)3′-GUUUCGGAUUGGAGUGUUGGAACCGAC-5′ (SEQ ID NO: 3515) MYC-m2069 Target:5′-CAAAGCCTAACCTCACAACCTTGGCTG-3′ (SEQ ID NO: 3659)5′-GCUUUGGGACUGUAAGCUUCAGCca-3′ (SEQ ID NO: 3372)3′-CCCGAAACCCUGACAUUCGAAGUCGGU-5′ (SEQ ID NO: 3516) MYC-m2096 Target:5′-GGGCTTTGGGACTGTAAGCTTCAGCCA-3′ (SEQ ID NO: 3660)5′-GACUGUAAGCUUCAGCCAUAAUUtt-3′ (SEQ ID NO: 3373)3′-CCCUGACAUUCGAAGUCGGUAUUAAAA-5′ (SEQ ID NO: 3517) MYC-m2103 Target:5′-GGGACTGTAAGCTTCAGCCATAATTTT-3′ (SEQ ID NO: 3661)5′-AGCUUCAGCCAUAAUUUUAACUGcc-3′ (SEQ ID NO: 3374)3′-AUUCGAAGUCGGUAUUAAAAUUGACGG-5′ (SEQ ID NO: 3518) MYC-m2110 Target:5′-TAAGCTTCAGCCATAATTTTAACTGCC-3′ (SEQ ID NO: 3662)5′-GCCAUAAUUUUAACUGCCUCAAAct-3′ (SEQ ID NO: 3375)3′-GUCGGUAUUAAAAUUGACGGAGUUUGA-5′ (SEQ ID NO: 3519) MYC-m2117 Target:5′-CAGCCATAATTTTAACTGCCTCAAACT-3′ (SEQ ID NO: 3663)5′-UUUAACUGCCUCAAACUUAAAUAgt-3′ (SEQ ID NO: 3376)3′-UAAAAUUGACGGAGUUUGAAUUUAUCA-5′ (SEQ ID NO: 3520) MYC-m2125 Target:5′-ATTTTAACTGCCTCAAACTTAAATAGT-3′ (SEQ ID NO: 3664)5′-UGCCUCAAACUUAAAUAGUAUAAaa-3′ (SEQ ID NO: 3377)3′-UGACGGAGUUUGAAUUUAUCAUAUUUU-5′ (SEQ ID NO: 3521) MYC-m2131 Target:5′-ACTGCCTCAAACTTAAATAGTATAAAA-3′ (SEQ ID NO: 3665)5′-CAAACUUAAAUAGUAUAAAAGAAct-3′ (SEQ ID NO: 3378)3′-GAGUUUGAAUUUAUCAUAUUUUCUUGA-5′ (SEQ ID NO: 3522) MYC-m2136 Target:5′-CTCAAACTTAAATAGTATAAAAGAACT-3′ (SEQ ID NO: 3666)5′-AAAUAGUAUAAAAGAACUUUUUUtt-3′ (SEQ ID NO: 3379)3′-AAUUUAUCAUAUUUUCUUGAAAAAAAA-5′ (SEQ ID NO: 3523) MYC-m2143 Target:5′-TTAAATAGTATAAAAGAACTTTTTTTT-3′ (SEQ ID NO: 3667)5′-UAUAAAAGAACUUUUUUUUAUGCtt-3′ (SEQ ID NO: 3380)3′-UCAUAUUUUCUUGAAAAAAAAUACGAA-5′ (SEQ ID NO: 3524) MYC-m2149 Target:5′-AGTATAAAAGAACTTTTTTTTATGCTT-3′ (SEQ ID NO: 3668)5′-AAGAACUUUUUUUUAUGCUUCCCat-3′ (SEQ ID NO: 3381)3′-UUUUCUUGAAAAAAAAUACGAAGGGUA-5′ (SEQ ID NO: 3525) MYC-m2154 Target:5′-AAAAGAACTTTTTTTTATGCTTCCCAT-3′ (SEQ ID NO: 3669)5′-CUUUUUUUUAUGCUUCCCAUCUUtt-3′ (SEQ ID NO: 3382)3′-UUGAAAAAAAAUACGAAGGGUAGAAAA-5′ (SEQ ID NO: 3526) MYC-m2159 Target:5′-AACTTTTTTTTATGCTTCCCATCTTTT-3′ (SEQ ID NO: 3670)5′-UUAUGCUUCCCAUCUUUUUUCUUtt-3′ (SEQ ID NO: 3383)3′-AAAAUACGAAGGGUAGAAAAAAGAAAA-5′ (SEQ ID NO: 3527) MYC-m2166 Target:5′-TTTTATGCTTCCCATCTTTTTTCTTTT-3′ (SEQ ID NO: 3671)5′-CUUCCCAUCUUUUUUCUUUUUCCtt-3′ (SEQ ID NO: 3384)3′-ACGAAGGGUAGAAAAAAGAAAAAGGAA-5′ (SEQ ID NO: 3528) MYC-m2171 Target:5′-TGCTTCCCATCTTTTTTCTTTTTCCTT-3′ (SEQ ID NO: 3672)5′-AUCUUUUUUCUUUUUCCUUUUAAca-3′ (SEQ ID NO: 3385)3′-GGUAGAAAAAAGAAAAAGGAAAAUUGU-5′ (SEQ ID NO: 3529) MYC-m2177 Target:5′-CCATCTTTTTTCTTTTTCCTTTTAACA-3′ (SEQ ID NO: 3673)5′-UUUUUCCUUUUAACAGAUUUGUAtt-3′ (SEQ ID NO: 3386)3′-AGAAAAAGGAAAAUUGUCUAAACAUAA-5′ (SEQ ID NO: 3530) MYC-m2187 Target:5′-TCTTTTTCCTTTTAACAGATTTGTATT-3′ (SEQ ID NO: 3674)5′-UUUUAACAGAUUUGUAUUUAAUUgt-3′ (SEQ ID NO: 3387)3′-GGAAAAUUGUCUAAACAUAAAUUAACA-5′ (SEQ ID NO: 3531) MYC-m2194 Target:5′-CCTTTTAACAGATTTGTATTTAATTGT-3′ (SEQ ID NO: 3675)5′-CAGAUUUGUAUUUAAUUGUUUUUtt-3′ (SEQ ID NO: 3388)3′-UUGUCUAAACAUAAAUUAACAAAAAAA-5′ (SEQ ID NO: 3532) MYC-m2200 Target:5′-AACAGATTTGTATTTAATTGTTTTTTT-3′ (SEQ ID NO: 3676)5′-UAUUUAAUUGUUUUUUUAAAAAAat-3′ (SEQ ID NO: 3389)3′-ACAUAAAUUAACAAAAAAAUUUUUUUA-5′ (SEQ ID NO: 3533) MYC-m2208 Target:5′-TGTATTTAATTGTTTTTTTAAAAAAAT-3′ (SEQ ID NO: 3677)5′-GUUUUUUUAAAAAAAUCUUAAAAtc-3′ (SEQ ID NO: 3390)3′-AACAAAAAAAUUUUUUUAGAAUUUUAG-5′ (SEQ ID NO: 3534) MYC-m2217 Target:5′-TTGTTTTTTTAAAAAAATCTTAAAATC-3′ (SEQ ID NO: 3678)5′-UAAAAAAAUCUUAAAAUCUAUCCaa-3′ (SEQ ID NO: 3391)3′-AAAUUUUUUUAGAAUUUUAGAUAGGUU-5′ (SEQ ID NO: 3535) MYC-m2224 Target:5′-TTTAAAAAAATCTTAAAATCTATCCAA-3′ (SEQ ID NO: 3679)5′-AAAUCUUAAAAUCUAUCCAAUUUtc-3′ (SEQ ID NO: 3392)3′-UUUUUAGAAUUUUAGAUAGGUUAAAAG-5′ (SEQ ID NO: 3536) MYC-m2229 Target:5′-AAAAATCTTAAAATCTATCCAATTTTC-3′ (SEQ ID NO: 3680)5′-AAAAUCUAUCCAAUUUUCCCAUGta-3′ (SEQ ID NO: 3393)3′-AAUUUUAGAUAGGUUAAAAGGGUACAU-5′ (SEQ ID NO: 3537) MYC-m2236 Target:5′-TTAAAATCTATCCAATTTTCCCATGTA-3′ (SEQ ID NO: 3681)5′-CUAUCCAAUUUUCCCAUGUAAAUag-3′ (SEQ ID NO: 3394)3′-UAGAUAGGUUAAAAGGGUACAUUUAUC-5′ (SEQ ID NO: 3538) MYC-m2241 Target:5′-ATCTATCCAATTTTCCCATGTAAATAG-3′ (SEQ ID NO: 3682)5′-CAUGUAAAUAGGGCCUUGAAAUGta-3′ (SEQ ID NO: 3395)3′-GGGUACAUUUAUCCCGGAACUUUACAU-5′ (SEQ ID NO: 3539) MYC-m2255 Target:5′-CCCATGTAAATAGGGCCTTGAAATGTA-3′ (SEQ ID NO: 3683)5′-AAAUAGGGCCUUGAAAUGUAAAUaa-3′ (SEQ ID NO: 3396)3′-CAUUUAUCCCGGAACUUUACAUUUAUU-5′ (SEQ ID NO: 3540) MYC-m2260 Target:5′-GTAAATAGGGCCTTGAAATGTAAATAA-3′ (SEQ ID NO: 3684)5′-GGGCCUUGAAAUGUAAAUAACUUta-3′ (SEQ ID NO: 3397)3′-AUCCCGGAACUUUACAUUUAUUGAAAU-5′ (SEQ ID NO: 3541) MYC-m2265 Target:5′-TAGGGCCTTGAAATGTAAATAACTTTA-3′ (SEQ ID NO: 3685)5′-UUGAAAUGUAAAUAACUUUAAUAaa-3′ (SEQ ID NO: 3398)3′-GGAACUUUACAUUUAUUGAAAUUAUUU-5′ (SEQ ID NO: 3542) MYC-m2270 Target:5′-CCTTGAAATGTAAATAACTTTAATAAA-3′ (SEQ ID NO: 3686)5′-UUUAAUAAAACGUUUAUAACAGUta-3′ (SEQ ID NO: 3399)3′-UGAAAUUAUUUUGCAAAUAUUGUCAAU-5′ (SEQ ID NO: 3543) MYC-m2286 Target:5′-ACTTTAATAAAACGTTTATAACAGTTA-3′ (SEQ ID NO: 3687)5′-UAAAACGUUUAUAACAGUUACAAaa-3′ (SEQ ID NO: 3400)3′-UUAUUUUGCAAAUAUUGUCAAUGUUUU-5′ (SEQ ID NO: 3544) MYC-m2291 Target:5′-AATAAAACGTTTATAACAGTTACAAAA-3′ (SEQ ID NO: 3688)5′-CGUUUAUAACAGUUACAAAAGAUtt-3′ (SEQ ID NO: 3401)3′-UUGCAAAUAUUGUCAAUGUUUUCUAAA-5′ (SEQ ID NO: 3545) MYC-m2296 Target:5′-AACGTTTATAACAGTTACAAAAGATTT-3′ (SEQ ID NO: 3689)5′-CAGUUACAAAAGAUUUUAAGACAtg-3′ (SEQ ID NO: 3402)3′-UUGUCAAUGUUUUCUAAAAUUCUGUAC-5′ (SEQ ID NO: 3546) MYC-m2305 Target:5′-AACAGTTACAAAAGATTTTAAGACATG-3′ (SEQ ID NO: 3690)5′-CAAAAGAUUUUAAGACAUGUACCat-3′ (SEQ ID NO: 3403)3′-AUGUUUUCUAAAAUUCUGUACAUGGUA-5′ (SEQ ID NO: 3547) MYC-m2311 Target:5′-TACAAAAGATTTTAAGACATGTACCAT-3′ (SEQ ID NO: 3691)5′-AUUUUAAGACAUGUACCAUAAUUtt-3′ (SEQ ID NO: 3404)3′-UCUAAAAUUCUGUACAUGGUAUUAAAA-5′ (SEQ ID NO: 3548) MYC-m2317 Target:5′-AGATTTTAAGACATGTACCATAATTTT-3′ (SEQ ID NO: 3692)5′-GACAUGUACCAUAAUUUUUUUUAtt-3′ (SEQ ID NO: 3405)3′-UUCUGUACAUGGUAUUAAAAAAAAUAA-5′ (SEQ ID NO: 3549) MYC-m2324 Target:5′-AAGACATGTACCATAATTTTTTTTATT-3′ (SEQ ID NO: 3693)5′-CAUAAUUUUUUUUAUUUAAAGACat-3′ (SEQ ID NO: 3406)3′-UGGUAUUAAAAAAAAUAAAUUUCUGUA-5′ (SEQ ID NO: 3550) MYC-m2333 Target:5′-ACCATAATTTTTTTTATTTAAAGACAT-3′ (SEQ ID NO: 3694)5′-UUUUUUUUAUUUAAAGACAUUUUca-3′ (SEQ ID NO: 3407)3′-UUAAAAAAAAUAAAUUUCUGUAAAAGU-5′ (SEQ ID NO: 3551) MYC-m2338 Target:5′-AATTTTTTTTATTTAAAGACATTTTCA-3′ (SEQ ID NO: 3695)5′-AUUUAAAGACAUUUUCAUUUUUAaa-3′ (SEQ ID NO: 3408)3′-AAUAAAUUUCUGUAAAAGUAAAAAUUU-5′ (SEQ ID NO: 3552) MYC-m2346 Target:5′-TTATTTAAAGACATTTTCATTTTTAAA-3′ (SEQ ID NO: 3696)5′-AAGACAUUUUCAUUUUUAAAGUUga-3′ (SEQ ID NO: 3409)3′-AUUUCUGUAAAAGUAAAAAUUUCAACU-5′ (SEQ ID NO: 3553) MYC-m2351 Target:5′-TAAAGACATTTTCATTTTTAAAGTTGA-3′ (SEQ ID NO: 3697)5′-AUUUUCAUUUUUAAAGUUGAUUUtt-3′ (SEQ ID NO: 3410)3′-UGUAAAAGUAAAAAUUUCAACUAAAAA-5′ (SEQ ID NO: 3554) MYC-m2356 Target:5′-ACATTTTCATTTTTAAAGTTGATTTTT-3′ (SEQ ID NO: 3698)5′-AUUUUUAAAGUUGAUUUUUUUCUat-3′ (SEQ ID NO: 3411)3′-AGUAAAAAUUUCAACUAAAAAAAGAUA-5′ (SEQ ID NO: 3555) MYC-m2362 Target:5′-TCATTTTTAAAGTTGATTTTTTTCTAT-3′ (SEQ ID NO: 3699)5′-UAUUGUUUUUAGAAAAAAAUAAAat-3′ (SEQ ID NO: 3412)3′-AGAUAACAAAAAUCUUUUUUUAUUUUA-5′ (SEQ ID NO: 3556) MYC-m2384 Target:5′-TCTATTGTTTTTAGAAAAAAATAAAAT-3′ (SEQ ID NO: 3700)5′-UUUUAGAAAAAAAUAAAAUAAUUgg-3′ (SEQ ID NO: 3413)3′-CAAAAAUCUUUUUUUAUUUUAUUAACC-5′ (SEQ ID NO: 3557) MYC-m2390 Target:5′-GTTTTTAGAAAAAAATAAAATAATTGG-3′ (SEQ ID NO: 3701)5′-AAAAAAUAAAAUAAUUGGAAAAAat-3′ (SEQ ID NO: 3414)3′-CUUUUUUUAUUUUAUUAACCUUUUUUA-5′ (SEQ ID NO: 3558) MYC-m2397 Target:5′-GAAAAAAATAAAATAATTGGAAAAAAT-3′ (SEQ ID NO: 3702)

TABLE 5 DsiRNA Target Sequences (21mers) In MYC mRNA MYC-94 21 ntTarget: 5′-CUCGAGAAGGGCAGGGCUUCU-3′ (SEQ ID NO: 1309) MYC-178 21 ntTarget: 5′-GGGCUUUAUCUAACUCGCUGU-3′ (SEQ ID NO: 1310) MYC-365 21 ntTarget: 5′-AACCCUUGCCGCAUCCACGAA-3′ (SEQ ID NO: 1311) MYC-370 21 ntTarget: 5′-UUGCCGCAUCCACGAAACUUU-3′ (SEQ ID NO: 1312) MYC-376 21 ntTarget: 5′-CAUCCACGAAACUUUGCCCAU-3′ (SEQ ID NO: 1313) MYC-403 21 ntTarget: 5′-GGGCGGGCACUUUGCACUGGA-3′ (SEQ ID NO: 1314) MYC-409 21 ntTarget: 5′-GCACUUUGCACUGGAACUUAC-3′ (SEQ ID NO: 1315) MYC-417 21 ntTarget: 5′-CACUGGAACUUACAACACCCG-3′ (SEQ ID NO: 1316) MYC-535 21 ntTarget: 5′-UUGCAGCUGCUUAGACGCUGG-3′ (SEQ ID NO: 1317) MYC-541 21 ntTarget: 5′-CUGCUUAGACGCUGGAUUUUU-3′ (SEQ ID NO: 1318) MYC-548 21 ntTarget: 5′-GACGCUGGAUUUUUUUCGGGU-3′ (SEQ ID NO: 1319) MYC-553 21 ntTarget: 5′-UGGAUUUUUUUCGGGUAGUGG-3′ (SEQ ID NO: 1320) MYC-562 21 ntTarget: 5′-UUCGGGUAGUGGAAAACCAGC-3′ (SEQ ID NO: 1321) MYC-601 21 ntTarget: 5′-CCCUCAACGUUAGCUUCACCA-3′ (SEQ ID NO: 1322) MYC-607 21 ntTarget: 5′-ACGUUAGCUUCACCAACAGGA-3′ (SEQ ID NO: 1323) MYC-643 21 ntTarget: 5′-ACGACUCGGUGCAGCCGUAUU-3′ (SEQ ID NO: 1324) MYC-651 21 ntTarget: 5′-GUGCAGCCGUAUUUCUACUGC-3′ (SEQ ID NO: 1325) MYC-676 21 ntTarget: 5′-AGGAGGAGAACUUCUACCAGC-3′ (SEQ ID NO: 1326) MYC-731 21 ntTarget: 5′-CAGCGAGGAUAUCUGGAAGAA-3′ (SEQ ID NO: 1327) MYC-816 21 ntTarget: 5′-UACGUUGCGGUCACACCCUUC-3′ (SEQ ID NO: 1328) MYC-920 21 ntTarget: 5′-AGACAUGGUGAACCAGAGUUU-3′ (SEQ ID NO: 1329) MYC-949 21 ntTarget: 5′-ACCCGGACGACGAGACCUUCA-3′ (SEQ ID NO: 1330) MYC-958 21 ntTarget: 5′-ACGAGACCUUCAUCAAAAACA-3′ (SEQ ID NO: 1331) MYC-970 21 ntTarget: 5′-UCAAAAACAUCAUCAUCCAGG-3′ (SEQ ID NO: 1332) MYC-987 21 ntTarget: 5′-CAGGACUGUAUGUGGAGCGGC-3′ (SEQ ID NO: 1333) MYC-1104 21 ntTarget: 5′-GUCUGCUCCACCUCCAGCUUG-3′ (SEQ ID NO: 1334) MYC-1111 21 ntTarget: 5′-CCACCUCCAGCUUGUACCUGC-3′ (SEQ ID NO: 1335) MYC-1116 21 ntTarget: 5′-UCCAGCUUGUACCUGCAGGAU-3′ (SEQ ID NO: 1336) MYC-1210 21 ntTarget: 5′-CCAAGUCCUGCGCCUCGCAAG-3′ (SEQ ID NO: 1337) MYC-1340 21 ntTarget: 5′-CAGCAGCGACUCUGAGGAGGA-3′ (SEQ ID NO: 1338) MYC-1346 21 ntTarget: 5′-CGACUCUGAGGAGGAACAAGA-3′ (SEQ ID NO: 1339) MYC-1351 21 ntTarget: 5′-CUGAGGAGGAACAAGAAGAUG-3′ (SEQ ID NO: 1340) MYC-1358 21 ntTarget: 5′-GGAACAAGAAGAUGAGGAAGA-3′ (SEQ ID NO: 1341) MYC-1364 21 ntTarget: 5′-AGAAGAUGAGGAAGAAAUCGA-3′ (SEQ ID NO: 1342) MYC-1370 21 ntTarget: 5′-UGAGGAAGAAAUCGAUGUUGU-3′ (SEQ ID NO: 1343) MYC-1376 21 ntTarget: 5′-AGAAAUCGAUGUUGUUUCUGU-3′ (SEQ ID NO: 1344) MYC-1382 21 ntTarget: 5′-CGAUGUUGUUUCUGUGGAAAA-3′ (SEQ ID NO: 1345) MYC-1401 21 ntTarget: 5′-AAGAGGCAGGCUCCUGGCAAA-3′ (SEQ ID NO: 1346) MYC-1406 21 ntTarget: 5′-GCAGGCUCCUGGCAAAAGGUC-3′ (SEQ ID NO: 1347) MYC-1411 21 ntTarget: 5′-CUCCUGGCAAAAGGUCAGAGU-3′ (SEQ ID NO: 1348) MYC-1416 21 ntTarget: 5′-GGCAAAAGGUCAGAGUCUGGA-3′ (SEQ ID NO: 1349) MYC-1421 21 ntTarget: 5′-AAGGUCAGAGUCUGGAUCACC-3′ (SEQ ID NO: 1350) MYC-1457 21 ntTarget: 5′-CAGCAAACCUCCUCACAGCCC-3′ (SEQ ID NO: 1351) MYC-1465 21 ntTarget: 5′-CUCCUCACAGCCCACUGGUCC-3′ (SEQ ID NO: 1352) MYC-1531 21 ntTarget: 5′-CUCCCUCCACUCGGAAGGACU-3′ (SEQ ID NO: 1353) MYC-1538 21 ntTarget: 5′-CACUCGGAAGGACUAUCCUGC-3′ (SEQ ID NO: 1354) MYC-1550 21 ntTarget: 5′-CUAUCCUGCUGCCAAGAGGGU-3′ (SEQ ID NO: 1355) MYC-1555 21 ntTarget: 5′-CUGCUGCCAAGAGGGUCAAGU-3′ (SEQ ID NO: 1356) MYC-1560 21 ntTarget: 5′-GCCAAGAGGGUCAAGUUGGAC-3′ (SEQ ID NO: 1357) MYC-1565 21 ntTarget: 5′-GAGGGUCAAGUUGGACAGUGU-3′ (SEQ ID NO: 1358) MYC-1570 21 ntTarget: 5′-UCAAGUUGGACAGUGUCAGAG-3′ (SEQ ID NO: 1359) MYC-1575 21 ntTarget: 5′-UUGGACAGUGUCAGAGUCCUG-3′ (SEQ ID NO: 1360) MYC-1584 21 ntTarget: 5′-GUCAGAGUCCUGAGACAGAUC-3′ (SEQ ID NO: 1361) MYC-1593 21 ntTarget: 5′-CUGAGACAGAUCAGCAACAAC-3′ (SEQ ID NO: 1362) MYC-1599 21 ntTarget: 5′-CAGAUCAGCAACAACCGAAAA-3′ (SEQ ID NO: 1363) MYC-1634 21 ntTarget: 5′-GUCCUCGGACACCGAGGAGAA-3′ (SEQ ID NO: 1364) MYC-1639 21 ntTarget: 5′-CGGACACCGAGGAGAAUGUCA-3′ (SEQ ID NO: 1365) MYC-1687 21 ntTarget: 5′-GCCAGAGGAGGAACGAGCUAA-3′ (SEQ ID NO: 1366) MYC-1693 21 ntTarget: 5′-GGAGGAACGAGCUAAAACGGA-3′ (SEQ ID NO: 1367) MYC-1698 21 ntTarget: 5′-AACGAGCUAAAACGGAGCUUU-3′ (SEQ ID NO: 1368) MYC-1704 21 ntTarget: 5′-CUAAAACGGAGCUUUUUUGCC-3′ (SEQ ID NO: 1369) MYC-1709 21 ntTarget: 5′-ACGGAGCUUUUUUGCCCUGCG-3′ (SEQ ID NO: 1370) MYC-1729 21 ntTarget: 5′-GUGACCAGAUCCCGGAGUUGG-3′ (SEQ ID NO: 1371) MYC-1734 21 ntTarget: 5′-CAGAUCCCGGAGUUGGAAAAC-3′ (SEQ ID NO: 1372) MYC-1739 21 ntTarget: 5′-CCCGGAGUUGGAAAACAAUGA-3′ (SEQ ID NO: 1373) MYC-1769 21 ntTarget: 5′-CAAGGUAGUUAUCCUUAAAAA-3′ (SEQ ID NO: 1374) MYC-1774 21 ntTarget: 5′-UAGUUAUCCUUAAAAAAGCCA-3′ (SEQ ID NO: 1375) MYC-1779 21 ntTarget: 5′-AUCCUUAAAAAAGCCACAGCA-3′ (SEQ ID NO: 1376) MYC-1784 21 ntTarget: 5′-UAAAAAAGCCACAGCAUACAU-3′ (SEQ ID NO: 1377) MYC-1789 21 ntTarget: 5′-AAGCCACAGCAUACAUCCUGU-3′ (SEQ ID NO: 1378) MYC-1795 21 ntTarget: 5′-CAGCAUACAUCCUGUCCGUCC-3′ (SEQ ID NO: 1379) MYC-1803 21 ntTarget: 5′-AUCCUGUCCGUCCAAGCAGAG-3′ (SEQ ID NO: 1380) MYC-1808 21 ntTarget: 5′-GUCCGUCCAAGCAGAGGAGCA-3′ (SEQ ID NO: 1381) MYC-1816 21 ntTarget: 5′-AAGCAGAGGAGCAAAAGCUCA-3′ (SEQ ID NO: 1382) MYC-1823 21 ntTarget: 5′-GGAGCAAAAGCUCAUUUCUGA-3′ (SEQ ID NO: 1383) MYC-1828 21 ntTarget: 5′-AAAAGCUCAUUUCUGAAGAGG-3′ (SEQ ID NO: 1384) MYC-1834 21 ntTarget: 5′-UCAUUUCUGAAGAGGACUUGU-3′ (SEQ ID NO: 1385) MYC-1840 21 ntTarget: 5′-CUGAAGAGGACUUGUUGCGGA-3′ (SEQ ID NO: 1386) MYC-1845 21 ntTarget: 5′-GAGGACUUGUUGCGGAAACGA-3′ (SEQ ID NO: 1387) MYC-1850 21 ntTarget: 5′-CUUGUUGCGGAAACGACGAGA-3′ (SEQ ID NO: 1388) MYC-1855 21 ntTarget: 5′-UGCGGAAACGACGAGAACAGU-3′ (SEQ ID NO: 1389) MYC-1882 21 ntTarget: 5′-ACAAACUUGAACAGCUACGGA-3′ (SEQ ID NO: 1390) MYC-1888 21 ntTarget: 5′-UUGAACAGCUACGGAACUCUU-3′ (SEQ ID NO: 1391) MYC-1893 21 ntTarget: 5′-CAGCUACGGAACUCUUGUGCG-3′ (SEQ ID NO: 1392) MYC-1900 21 ntTarget: 5′-GGAACUCUUGUGCGUAAGGAA-3′ (SEQ ID NO: 1393) MYC-1906 21 ntTarget: 5′-CUUGUGCGUAAGGAAAAGUAA-3′ (SEQ ID NO: 1394) MYC-1911 21 ntTarget: 5′-GCGUAAGGAAAAGUAAGGAAA-3′ (SEQ ID NO: 1395) MYC-1921 21 ntTarget: 5′-AAGUAAGGAAAACGAUUCCUU-3′ (SEQ ID NO: 1396) MYC-1926 21 ntTarget: 5′-AGGAAAACGAUUCCUUCUAAC-3′ (SEQ ID NO: 1397) MYC-1931 21 ntTarget: 5′-AACGAUUCCUUCUAACAGAAA-3′ (SEQ ID NO: 1398) MYC-1937 21 ntTarget: 5′-UCCUUCUAACAGAAAUGUCCU-3′ (SEQ ID NO: 1399) MYC-1944 21 ntTarget: 5′-AACAGAAAUGUCCUGAGCAAU-3′ (SEQ ID NO: 1400) MYC-1953 21 ntTarget: 5′-GUCCUGAGCAAUCACCUAUGA-3′ (SEQ ID NO: 1401) MYC-1959 21 ntTarget: 5′-AGCAAUCACCUAUGAACUUGU-3′ (SEQ ID NO: 1402) MYC-1965 21 ntTarget: 5′-CACCUAUGAACUUGUUUCAAA-3′ (SEQ ID NO: 1403) MYC-1970 21 ntTarget: 5′-AUGAACUUGUUUCAAAUGCAU-3′ (SEQ ID NO: 1404) MYC-1976 21 ntTarget: 5′-UUGUUUCAAAUGCAUGAUCAA-3′ (SEQ ID NO: 1405) MYC-1981 21 ntTarget: 5′-UCAAAUGCAUGAUCAAAUGCA-3′ (SEQ ID NO: 1406) MYC-1989 21 ntTarget: 5′-AUGAUCAAAUGCAACCUCACA-3′ (SEQ ID NO: 1407) MYC-1994 21 ntTarget: 5′-CAAAUGCAACCUCACAACCUU-3′ (SEQ ID NO: 1408) MYC-2001 21 ntTarget: 5′-AACCUCACAACCUUGGCUGAG-3′ (SEQ ID NO: 1409) MYC-2006 21 ntTarget: 5′-CACAACCUUGGCUGAGUCUUG-3′ (SEQ ID NO: 1410) MYC-2013 21 ntTarget: 5′-UUGGCUGAGUCUUGAGACUGA-3′ (SEQ ID NO: 1411) MYC-2019 21 ntTarget: 5′-GAGUCUUGAGACUGAAAGAUU-3′ (SEQ ID NO: 1412) MYC-2026 21 ntTarget: 5′-GAGACUGAAAGAUUUAGCCAU-3′ (SEQ ID NO: 1413) MYC-2031 21 ntTarget: 5′-UGAAAGAUUUAGCCAUAAUGU-3′ (SEQ ID NO: 1414) MYC-2040 21 ntTarget: 5′-UAGCCAUAAUGUAAACUGCCU-3′ (SEQ ID NO: 1415) MYC-2048 21 ntTarget: 5′-AUGUAAACUGCCUCAAAUUGG-3′ (SEQ ID NO: 1416) MYC-2054 21 ntTarget: 5′-ACUGCCUCAAAUUGGACUUUG-3′ (SEQ ID NO: 1417) MYC-2059 21 ntTarget: 5′-CUCAAAUUGGACUUUGGGCAU-3′ (SEQ ID NO: 1418) MYC-2066 21 ntTarget: 5′-UGGACUUUGGGCAUAAAAGAA-3′ (SEQ ID NO: 1419) MYC-2073 21 ntTarget: 5′-UGGGCAUAAAAGAACUUUUUU-3′ (SEQ ID NO: 1420) MYC-2078 21 ntTarget: 5′-AUAAAAGAACUUUUUUAUGCU-3′ (SEQ ID NO: 1421) MYC-2083 21 ntTarget: 5′-AGAACUUUUUUAUGCUUACCA-3′ (SEQ ID NO: 1422) MYC-2089 21 ntTarget: 5′-UUUUUAUGCUUACCAUCUUUU-3′ (SEQ ID NO: 1423) MYC-2094 21 ntTarget: 5′-AUGCUUACCAUCUUUUUUUUU-3′ (SEQ ID NO: 1424) MYC-2099 21 ntTarget: 5′-UACCAUCUUUUUUUUUUCUUU-3′ (SEQ ID NO: 1425) MYC-2105 21 ntTarget: 5′-CUUUUUUUUUUCUUUAACAGA-3′ (SEQ ID NO: 1426) MYC-2114 21 ntTarget: 5′-UUCUUUAACAGAUUUGUAUUU-3′ (SEQ ID NO: 1427) MYC-2120 21 ntTarget: 5′-AACAGAUUUGUAUUUAAGAAU-3′ (SEQ ID NO: 1428) MYC-2128 21 ntTarget: 5′-UGUAUUUAAGAAUUGUUUUUA-3′ (SEQ ID NO: 1429) MYC-2135 21 ntTarget: 5′-AAGAAUUGUUUUUAAAAAAUU-3′ (SEQ ID NO: 1430) MYC-2167 21 ntTarget: 5′-ACAAUGUUUCUCUGUAAAUAU-3′ (SEQ ID NO: 1431) MYC-2176 21 ntTarget: 5′-CUCUGUAAAUAUUGCCAUUAA-3′ (SEQ ID NO: 1432) MYC-2181 21 ntTarget: 5′-UAAAUAUUGCCAUUAAAUGUA-3′ (SEQ ID NO: 1433) MYC-2188 21 ntTarget: 5′-UGCCAUUAAAUGUAAAUAACU-3′ (SEQ ID NO: 1434) MYC-2207 21 ntTarget: 5′-CUUUAAUAAAACGUUUAUAGC-3′ (SEQ ID NO: 1435) MYC-2233 21 ntTarget: 5′-CACAGAAUUUCAAUCCUAGUA-3′ (SEQ ID NO: 1436) MYC-2260 21 ntTarget: 5′-ACCUAGUAUUAUAGGUACUAU-3′ (SEQ ID NO: 1437) MYC-2267 21 ntTarget: 5′-AUUAUAGGUACUAUAAACCCU-3′ (SEQ ID NO: 1438) MYC-2274 21 ntTarget: 5′-GUACUAUAAACCCUAAUUUUU-3′ (SEQ ID NO: 1439) MYC-2282 21 ntTarget: 5′-AACCCUAAUUUUUUUUAUUUA-3′ (SEQ ID NO: 1440) MYC-2287 21 ntTarget: 5′-UAAUUUUUUUUAUUUAAGUAC-3′ (SEQ ID NO: 1441) MYC-2295 21 ntTarget: 5′-UUUAUUUAAGUACAUUUUGCU-3′ (SEQ ID NO: 1442) MYC-2300 21 ntTarget: 5′-UUAAGUACAUUUUGCUUUUUA-3′ (SEQ ID NO: 1443) MYC-2306 21 ntTarget: 5′-ACAUUUUGCUUUUUAAAGUUG-3′ (SEQ ID NO: 1444) MYC-2312 21 ntTarget: 5′-UGCUUUUUAAAGUUGAUUUUU-3′ (SEQ ID NO: 1445) MYC-2334 21 ntTarget: 5′-UCUAUUGUUUUUAGAAAAAAU-3′ (SEQ ID NO: 1446) MYC-2339 21 ntTarget: 5′-UGUUUUUAGAAAAAAUAAAAU-3′ (SEQ ID NO: 1447) MYC-2347 21 ntTarget: 5′-GAAAAAAUAAAAUAACUGGCA-3′ (SEQ ID NO: 1448) MYC-2355 21 ntTarget: 5′-AAAAUAACUGGCAAAUAUAUC-3′ (SEQ ID NO: 1449) MYC-2364 21 ntTarget: 5′-GGCAAAUAUAUCAUUGAGCCA-3′ (SEQ ID NO: 1450) MYC-2371 21 ntTarget: 5′-AUAUCAUUGAGCCAAAUCUUA-3′ (SEQ ID NO: 1451) MYC-2377 21 ntTarget: 5′-UUGAGCCAAAUCUUAAAAAAA-3′ (SEQ ID NO: 1452) MYC-188 21 ntTarget: 5′-UAACUCGCUGUAGUAAUUCCA-3′ (SEQ ID NO: 1453) MYC-189 21 ntTarget: 5′-AACUCGCUGUAGUAAUUCCAG-3′ (SEQ ID NO: 1454) MYC-190 21 ntTarget: 5′-ACUCGCUGUAGUAAUUCCAGC-3′ (SEQ ID NO: 1455) MYC-191 21 ntTarget: 5′-CUCGCUGUAGUAAUUCCAGCG-3′ (SEQ ID NO: 1456) MYC-192 21 ntTarget: 5′-UCGCUGUAGUAAUUCCAGCGA-3′ (SEQ ID NO: 1457) MYC-193 21 ntTarget: 5′-CGCUGUAGUAAUUCCAGCGAG-3′ (SEQ ID NO: 1458) MYC-194 21 ntTarget: 5′-GCUGUAGUAAUUCCAGCGAGA-3′ (SEQ ID NO: 1459) MYC-195 21 ntTarget: 5′-CUGUAGUAAUUCCAGCGAGAG-3′ (SEQ ID NO: 1460) MYC-612 21 ntTarget: 5′-AGCUUCACCAACAGGAACUAU-3′ (SEQ ID NO: 1461) MYC-613 21 ntTarget: 5′-GCUUCACCAACAGGAACUAUG-3′ (SEQ ID NO: 1462) MYC-614 21 ntTarget: 5′-CUUCACCAACAGGAACUAUGA-3′ (SEQ ID NO: 1463) MYC-615 21 ntTarget: 5′-UUCACCAACAGGAACUAUGAC-3′ (SEQ ID NO: 1464) MYC-616 21 ntTarget: 5′-UCACCAACAGGAACUAUGACC-3′ (SEQ ID NO: 1465) MYC-617 21 ntTarget: 5′-CACCAACAGGAACUAUGACCU-3′ (SEQ ID NO: 1466) MYC-618 21 ntTarget: 5′-ACCAACAGGAACUAUGACCUC-3′ (SEQ ID NO: 1467) MYC-619 21 ntTarget: 5′-CCAACAGGAACUAUGACCUCG-3′ (SEQ ID NO: 1468) MYC-620 21 ntTarget: 5′-CAACAGGAACUAUGACCUCGA-3′ (SEQ ID NO: 1469) MYC-621 21 ntTarget: 5′-AACAGGAACUAUGACCUCGAC-3′ (SEQ ID NO: 1470) MYC-622 21 ntTarget: 5′-ACAGGAACUAUGACCUCGACU-3′ (SEQ ID NO: 1471) MYC-623 21 ntTarget: 5′-CAGGAACUAUGACCUCGACUA-3′ (SEQ ID NO: 1472) MYC-624 21 ntTarget: 5′-AGGAACUAUGACCUCGACUAC-3′ (SEQ ID NO: 1473) MYC-625 21 ntTarget: 5′-GGAACUAUGACCUCGACUACG-3′ (SEQ ID NO: 1474) MYC-626 21 ntTarget: 5′-GAACUAUGACCUCGACUACGA-3′ (SEQ ID NO: 1475) MYC-627 21 ntTarget: 5′-AACUAUGACCUCGACUACGAC-3′ (SEQ ID NO: 1476) MYC-628 21 ntTarget: 5′-ACUAUGACCUCGACUACGACU-3′ (SEQ ID NO: 1477) MYC-629 21 ntTarget: 5′-CUAUGACCUCGACUACGACUC-3′ (SEQ ID NO: 1478) MYC-733 21 ntTarget: 5′-GCGAGGAUAUCUGGAAGAAAU-3′ (SEQ ID NO: 1479) MYC-734 21 ntTarget: 5′-CGAGGAUAUCUGGAAGAAAUU-3′ (SEQ ID NO: 1480) MYC-735 21 ntTarget: 5′-GAGGAUAUCUGGAAGAAAUUC-3′ (SEQ ID NO: 1481) MYC-736 21 ntTarget: 5′-AGGAUAUCUGGAAGAAAUUCG-3′ (SEQ ID NO: 1482) MYC-737 21 ntTarget: 5′-GGAUAUCUGGAAGAAAUUCGA-3′ (SEQ ID NO: 1483) MYC-738 21 ntTarget: 5′-GAUAUCUGGAAGAAAUUCGAG-3′ (SEQ ID NO: 1484) MYC-739 21 ntTarget: 5′-AUAUCUGGAAGAAAUUCGAGC-3′ (SEQ ID NO: 1485) MYC-740 21 ntTarget: 5′-UAUCUGGAAGAAAUUCGAGCU-3′ (SEQ ID NO: 1486) MYC-741 21 ntTarget: 5′-AUCUGGAAGAAAUUCGAGCUG-3′ (SEQ ID NO: 1487) MYC-742 21 ntTarget: 5′-UCUGGAAGAAAUUCGAGCUGC-3′ (SEQ ID NO: 1488) MYC-743 21 ntTarget: 5′-CUGGAAGAAAUUCGAGCUGCU-3′ (SEQ ID NO: 1489) MYC-784 21 ntTarget: 5′-CUAGCCGCCGCUCCGGGCUCU-3′ (SEQ ID NO: 1490) MYC-785 21 ntTarget: 5′-UAGCCGCCGCUCCGGGCUCUG-3′ (SEQ ID NO: 1491) MYC-786 21 ntTarget: 5′-AGCCGCCGCUCCGGGCUCUGC-3′ (SEQ ID NO: 1492) MYC-787 21 ntTarget: 5′-GCCGCCGCUCCGGGCUCUGCU-3′ (SEQ ID NO: 1493) MYC-788 21 ntTarget: 5′-CCGCCGCUCCGGGCUCUGCUC-3′ (SEQ ID NO: 1494) MYC-913 21 ntTarget: 5′-UGGGAGGAGACAUGGUGAACC-3′ (SEQ ID NO: 1495) MYC-914 21 ntTarget: 5′-GGGAGGAGACAUGGUGAACCA-3′ (SEQ ID NO: 1496) MYC-915 21 ntTarget: 5′-GGAGGAGACAUGGUGAACCAG-3′ (SEQ ID NO: 1497) MYC-916 21 ntTarget: 5′-GAGGAGACAUGGUGAACCAGA-3′ (SEQ ID NO: 1498) MYC-917 21 ntTarget: 5′-AGGAGACAUGGUGAACCAGAG-3′ (SEQ ID NO: 1499) MYC-952 21 ntTarget: 5′-CGGACGACGAGACCUUCAUCA-3′ (SEQ ID NO: 1500) MYC-953 21 ntTarget: 5′-GGACGACGAGACCUUCAUCAA-3′ (SEQ ID NO: 1501) MYC-973 21 ntTarget: 5′-AAAACAUCAUCAUCCAGGACU-3′ (SEQ ID NO: 1502) MYC-974 21 ntTarget: 5′-AAACAUCAUCAUCCAGGACUG-3′ (SEQ ID NO: 1503) MYC-975 21 ntTarget: 5′-AACAUCAUCAUCCAGGACUGU-3′ (SEQ ID NO: 1504) MYC-976 21 ntTarget: 5′-ACAUCAUCAUCCAGGACUGUA-3′ (SEQ ID NO: 1505) MYC-977 21 ntTarget: 5′-CAUCAUCAUCCAGGACUGUAU-3′ (SEQ ID NO: 1506) MYC-978 21 ntTarget: 5′-AUCAUCAUCCAGGACUGUAUG-3′ (SEQ ID NO: 1507) MYC-979 21 ntTarget: 5′-UCAUCAUCCAGGACUGUAUGU-3′ (SEQ ID NO: 1508) MYC-980 21 ntTarget: 5′-CAUCAUCCAGGACUGUAUGUG-3′ (SEQ ID NO: 1509) MYC-981 21 ntTarget: 5′-AUCAUCCAGGACUGUAUGUGG-3′ (SEQ ID NO: 1510) MYC-982 21 ntTarget: 5′-UCAUCCAGGACUGUAUGUGGA-3′ (SEQ ID NO: 1511) MYC-983 21 ntTarget: 5′-CAUCCAGGACUGUAUGUGGAG-3′ (SEQ ID NO: 1512) MYC-984 21 ntTarget: 5′-AUCCAGGACUGUAUGUGGAGC-3′ (SEQ ID NO: 1513) MYC-985 21 ntTarget: 5′-UCCAGGACUGUAUGUGGAGCG-3′ (SEQ ID NO: 1514) MYC-986 21 ntTarget: 5′-CCAGGACUGUAUGUGGAGCGG-3′ (SEQ ID NO: 1515) MYC-1033 21 ntTarget: 5′-CAGAGAAGCUGGCCUCCUACC-3′ (SEQ ID NO: 1516) MYC-1034 21 ntTarget: 5′-AGAGAAGCUGGCCUCCUACCA-3′ (SEQ ID NO: 1517) MYC-1035 21 ntTarget: 5′-GAGAAGCUGGCCUCCUACCAG-3′ (SEQ ID NO: 1518) MYC-1036 21 ntTarget: 5′-AGAAGCUGGCCUCCUACCAGG-3′ (SEQ ID NO: 1519) MYC-1037 21 ntTarget: 5′-GAAGCUGGCCUCCUACCAGGC-3′ (SEQ ID NO: 1520) MYC-1038 21 ntTarget: 5′-AAGCUGGCCUCCUACCAGGCU-3′ (SEQ ID NO: 1521) MYC-1039 21 ntTarget: 5′-AGCUGGCCUCCUACCAGGCUG-3′ (SEQ ID NO: 1522) MYC-1040 21 ntTarget: 5′-GCUGGCCUCCUACCAGGCUGC-3′ (SEQ ID NO: 1523) MYC-1041 21 ntTarget: 5′-CUGGCCUCCUACCAGGCUGCG-3′ (SEQ ID NO: 1524) MYC-1042 21 ntTarget: 5′-UGGCCUCCUACCAGGCUGCGC-3′ (SEQ ID NO: 1525) MYC-1043 21 ntTarget: 5′-GGCCUCCUACCAGGCUGCGCG-3′ (SEQ ID NO: 1526) MYC-1044 21 ntTarget: 5′-GCCUCCUACCAGGCUGCGCGC-3′ (SEQ ID NO: 1527) MYC-1045 21 ntTarget: 5′-CCUCCUACCAGGCUGCGCGCA-3′ (SEQ ID NO: 1528) MYC-1046 21 ntTarget: 5′-CUCCUACCAGGCUGCGCGCAA-3′ (SEQ ID NO: 1529) MYC-1047 21 ntTarget: 5′-UCCUACCAGGCUGCGCGCAAA-3′ (SEQ ID NO: 1530) MYC-1048 21 ntTarget: 5′-CCUACCAGGCUGCGCGCAAAG-3′ (SEQ ID NO: 1531) MYC-1049 21 ntTarget: 5′-CUACCAGGCUGCGCGCAAAGA-3′ (SEQ ID NO: 1532) MYC-1050 21 ntTarget: 5′-UACCAGGCUGCGCGCAAAGAC-3′ (SEQ ID NO: 1533) MYC-1051 21 ntTarget: 5′-ACCAGGCUGCGCGCAAAGACA-3′ (SEQ ID NO: 1534) MYC-1052 21 ntTarget: 5′-CCAGGCUGCGCGCAAAGACAG-3′ (SEQ ID NO: 1535) MYC-1053 21 ntTarget: 5′-CAGGCUGCGCGCAAAGACAGC-3′ (SEQ ID NO: 1536) MYC-1096 21 ntTarget: 5′-GCCACAGCGUCUGCUCCACCU-3′ (SEQ ID NO: 1537) MYC-1097 21 ntTarget: 5′-CCACAGCGUCUGCUCCACCUC-3′ (SEQ ID NO: 1538) MYC-1098 21 ntTarget: 5′-CACAGCGUCUGCUCCACCUCC-3′ (SEQ ID NO: 1539) MYC-1099 21 ntTarget: 5′-ACAGCGUCUGCUCCACCUCCA-3′ (SEQ ID NO: 1540) MYC-1100 21 ntTarget: 5′-CAGCGUCUGCUCCACCUCCAG-3′ (SEQ ID NO: 1541) MYC-1101 21 ntTarget: 5′-AGCGUCUGCUCCACCUCCAGC-3′ (SEQ ID NO: 1542) MYC-1189 21 ntTarget: 5′-CUCUCAACGACAGCAGCUCGC-3′ (SEQ ID NO: 1543) MYC-1190 21 ntTarget: 5′-UCUCAACGACAGCAGCUCGCC-3′ (SEQ ID NO: 1544) MYC-1191 21 ntTarget: 5′-CUCAACGACAGCAGCUCGCCC-3′ (SEQ ID NO: 1545) MYC-1192 21 ntTarget: 5′-UCAACGACAGCAGCUCGCCCA-3′ (SEQ ID NO: 1546) MYC-1193 21 ntTarget: 5′-CAACGACAGCAGCUCGCCCAA-3′ (SEQ ID NO: 1547) MYC-1315 21 ntTarget: 5′-UCCAUGAGGAGACACCGCCCA-3′ (SEQ ID NO: 1548) MYC-1316 21 ntTarget: 5′-CCAUGAGGAGACACCGCCCAC-3′ (SEQ ID NO: 1549) MYC-1317 21 ntTarget: 5′-CAUGAGGAGACACCGCCCACC-3′ (SEQ ID NO: 1550) MYC-1318 21 ntTarget: 5′-AUGAGGAGACACCGCCCACCA-3′ (SEQ ID NO: 1551) MYC-1319 21 ntTarget: 5′-UGAGGAGACACCGCCCACCAC-3′ (SEQ ID NO: 1552) MYC-1320 21 ntTarget: 5′-GAGGAGACACCGCCCACCACC-3′ (SEQ ID NO: 1553) MYC-1321 21 ntTarget: 5′-AGGAGACACCGCCCACCACCA-3′ (SEQ ID NO: 1554) MYC-1322 21 ntTarget: 5′-GGAGACACCGCCCACCACCAG-3′ (SEQ ID NO: 1555) MYC-1323 21 ntTarget: 5′-GAGACACCGCCCACCACCAGC-3′ (SEQ ID NO: 1556) MYC-1324 21 ntTarget: 5′-AGACACCGCCCACCACCAGCA-3′ (SEQ ID NO: 1557) MYC-1325 21 ntTarget: 5′-GACACCGCCCACCACCAGCAG-3′ (SEQ ID NO: 1558) MYC-1326 21 ntTarget: 5′-ACACCGCCCACCACCAGCAGC-3′ (SEQ ID NO: 1559) MYC-1327 21 ntTarget: 5′-CACCGCCCACCACCAGCAGCG-3′ (SEQ ID NO: 1560) MYC-1328 21 ntTarget: 5′-ACCGCCCACCACCAGCAGCGA-3′ (SEQ ID NO: 1561) MYC-1329 21 ntTarget: 5′-CCGCCCACCACCAGCAGCGAC-3′ (SEQ ID NO: 1562) MYC-1330 21 ntTarget: 5′-CGCCCACCACCAGCAGCGACU-3′ (SEQ ID NO: 1563) MYC-1331 21 ntTarget: 5′-GCCCACCACCAGCAGCGACUC-3′ (SEQ ID NO: 1564) MYC-1332 21 ntTarget: 5′-CCCACCACCAGCAGCGACUCU-3′ (SEQ ID NO: 1565) MYC-1333 21 ntTarget: 5′-CCACCACCAGCAGCGACUCUG-3′ (SEQ ID NO: 1566) MYC-1334 21 ntTarget: 5′-CACCACCAGCAGCGACUCUGA-3′ (SEQ ID NO: 1567) MYC-1360 21 ntTarget: 5′-AACAAGAAGAUGAGGAAGAAA-3′ (SEQ ID NO: 1568) MYC-1361 21 ntTarget: 5′-ACAAGAAGAUGAGGAAGAAAU-3′ (SEQ ID NO: 1569) MYC-1448 21 ntTarget: 5′-UGGAGGCCACAGCAAACCUCC-3′ (SEQ ID NO: 1570) MYC-1468 21 ntTarget: 5′-CUCACAGCCCACUGGUCCUCA-3′ (SEQ ID NO: 1571) MYC-1469 21 ntTarget: 5′-UCACAGCCCACUGGUCCUCAA-3′ (SEQ ID NO: 1572) MYC-1470 21 ntTarget: 5′-CACAGCCCACUGGUCCUCAAG-3′ (SEQ ID NO: 1573) MYC-1471 21 ntTarget: 5′-ACAGCCCACUGGUCCUCAAGA-3′ (SEQ ID NO: 1574) MYC-1472 21 ntTarget: 5′-CAGCCCACUGGUCCUCAAGAG-3′ (SEQ ID NO: 1575) MYC-1473 21 ntTarget: 5′-AGCCCACUGGUCCUCAAGAGG-3′ (SEQ ID NO: 1576) MYC-1474 21 ntTarget: 5′-GCCCACUGGUCCUCAAGAGGU-3′ (SEQ ID NO: 1577) MYC-1475 21 ntTarget: 5′-CCCACUGGUCCUCAAGAGGUG-3′ (SEQ ID NO: 1578) MYC-1476 21 ntTarget: 5′-CCACUGGUCCUCAAGAGGUGC-3′ (SEQ ID NO: 1579) MYC-1477 21 ntTarget: 5′-CACUGGUCCUCAAGAGGUGCC-3′ (SEQ ID NO: 1580) MYC-1478 21 ntTarget: 5′-ACUGGUCCUCAAGAGGUGCCA-3′ (SEQ ID NO: 1581) MYC-1479 21 ntTarget: 5′-CUGGUCCUCAAGAGGUGCCAC-3′ (SEQ ID NO: 1582) MYC-1480 21 ntTarget: 5′-UGGUCCUCAAGAGGUGCCACG-3′ (SEQ ID NO: 1583) MYC-1481 21 ntTarget: 5′-GGUCCUCAAGAGGUGCCACGU-3′ (SEQ ID NO: 1584) MYC-1482 21 ntTarget: 5′-GUCCUCAAGAGGUGCCACGUC-3′ (SEQ ID NO: 1585) MYC-1483 21 ntTarget: 5′-UCCUCAAGAGGUGCCACGUCU-3′ (SEQ ID NO: 1586) MYC-1711 21 ntTarget: 5′-GGAGCUUUUUUGCCCUGCGUG-3′ (SEQ ID NO: 1587) MYC-1712 21 ntTarget: 5′-GAGCUUUUUUGCCCUGCGUGA-3′ (SEQ ID NO: 1588) MYC-1713 21 ntTarget: 5′-AGCUUUUUUGCCCUGCGUGAC-3′ (SEQ ID NO: 1589) MYC-1714 21 ntTarget: 5′-GCUUUUUUGCCCUGCGUGACC-3′ (SEQ ID NO: 1590) MYC-1715 21 ntTarget: 5′-CUUUUUUGCCCUGCGUGACCA-3′ (SEQ ID NO: 1591) MYC-1716 21 ntTarget: 5′-UUUUUUGCCCUGCGUGACCAG-3′ (SEQ ID NO: 1592) MYC-1717 21 ntTarget: 5′-UUUUUGCCCUGCGUGACCAGA-3′ (SEQ ID NO: 1593) MYC-1718 21 ntTarget: 5′-UUUUGCCCUGCGUGACCAGAU-3′ (SEQ ID NO: 1594) MYC-1719 21 ntTarget: 5′-UUUGCCCUGCGUGACCAGAUC-3′ (SEQ ID NO: 1595) MYC-1720 21 ntTarget: 5′-UUGCCCUGCGUGACCAGAUCC-3′ (SEQ ID NO: 1596) MYC-1721 21 ntTarget: 5′-UGCCCUGCGUGACCAGAUCCC-3′ (SEQ ID NO: 1597) MYC-1856 21 ntTarget: 5′-GCGGAAACGACGAGAACAGUU-3′ (SEQ ID NO: 1598) MYC-1857 21 ntTarget: 5′-CGGAAACGACGAGAACAGUUG-3′ (SEQ ID NO: 1599) MYC-2115 21 ntTarget: 5′-UCUUUAACAGAUUUGUAUUUA-3′ (SEQ ID NO: 1600) MYC-2116 21 ntTarget: 5′-CUUUAACAGAUUUGUAUUUAA-3′ (SEQ ID NO: 1601) MYC-2193 21 ntTarget: 5′-UUAAAUGUAAAUAACUUUAAU-3′ (SEQ ID NO: 1602) MYC-2194 21 ntTarget: 5′-UAAAUGUAAAUAACUUUAAUA-3′ (SEQ ID NO: 1603) MYC-2195 21 ntTarget: 5′-AAAUGUAAAUAACUUUAAUAA-3′ (SEQ ID NO: 1604) MYC-2196 21 ntTarget: 5′-AAUGUAAAUAACUUUAAUAAA-3′ (SEQ ID NO: 1605) MYC-2197 21 ntTarget: 5′-AUGUAAAUAACUUUAAUAAAA-3′ (SEQ ID NO: 1606) MYC-2198 21 ntTarget: 5′-UGUAAAUAACUUUAAUAAAAC-3′ (SEQ ID NO: 1607) MYC-2199 21 ntTarget: 5′-GUAAAUAACUUUAAUAAAACG-3′ (SEQ ID NO: 1608) MYC-2200 21 ntTarget: 5′-UAAAUAACUUUAAUAAAACGU-3′ (SEQ ID NO: 1609) MYC-2201 21 ntTarget: 5′-AAAUAACUUUAAUAAAACGUU-3′ (SEQ ID NO: 1610) MYC-2202 21 ntTarget: 5′-AAUAACUUUAAUAAAACGUUU-3′ (SEQ ID NO: 1611) MYC-2203 21 ntTarget: 5′-AUAACUUUAAUAAAACGUUUA-3′ (SEQ ID NO: 1612) MYC-2204 21 ntTarget: 5′-UAACUUUAAUAAAACGUUUAU-3′ (SEQ ID NO: 1613) MYC-2205 21 ntTarget: 5′-AACUUUAAUAAAACGUUUAUA-3′ (SEQ ID NO: 1614) MYC-2313 21 ntTarget: 5′-GCUUUUUAAAGUUGAUUUUUU-3′ (SEQ ID NO: 1615) MYC-2314 21 ntTarget: 5′-CUUUUUAAAGUUGAUUUUUUU-3′ (SEQ ID NO: 1616) MYC-2315 21 ntTarget: 5′-UUUUUAAAGUUGAUUUUUUUC-3′ (SEQ ID NO: 1617) MYC-2316 21 ntTarget: 5′-UUUUAAAGUUGAUUUUUUUCU-3′ (SEQ ID NO: 1618) MYC-2317 21 ntTarget: 5′-UUUAAAGUUGAUUUUUUUCUA-3′ (SEQ ID NO: 1619) MYC-2318 21 ntTarget: 5′-UUAAAGUUGAUUUUUUUCUAU-3′ (SEQ ID NO: 1620) MYC-2319 21 ntTarget: 5′-UAAAGUUGAUUUUUUUCUAUU-3′ (SEQ ID NO: 1621) MYC-2320 21 ntTarget: 5′-AAAGUUGAUUUUUUUCUAUUG-3′ (SEQ ID NO: 1622) MYC-2321 21 ntTarget: 5′-AAGUUGAUUUUUUUCUAUUGU-3′ (SEQ ID NO: 1623) MYC-2322 21 ntTarget: 5′-AGUUGAUUUUUUUCUAUUGUU-3′ (SEQ ID NO: 1624) MYC-2323 21 ntTarget: 5′-GUUGAUUUUUUUCUAUUGUUU-3′ (SEQ ID NO: 1625) MYC-2324 21 ntTarget: 5′-UUGAUUUUUUUCUAUUGUUUU-3′ (SEQ ID NO: 1626) MYC-2325 21 ntTarget: 5′-UGAUUUUUUUCUAUUGUUUUU-3′ (SEQ ID NO: 1627) MYC-2326 21 ntTarget: 5′-GAUUUUUUUCUAUUGUUUUUA-3′ (SEQ ID NO: 1628) MYC-2327 21 ntTarget: 5′-AUUUUUUUCUAUUGUUUUUAG-3′ (SEQ ID NO: 1629) MYC-2328 21 ntTarget: 5′-UUUUUUUCUAUUGUUUUUAGA-3′ (SEQ ID NO: 1630) MYC-2329 21 ntTarget: 5′-UUUUUUCUAUUGUUUUUAGAA-3′ (SEQ ID NO: 1631) MYC-2330 21 ntTarget: 5′-UUUUUCUAUUGUUUUUAGAAA-3′ (SEQ ID NO: 1632) MYC-2331 21 ntTarget: 5′-UUUUCUAUUGUUUUUAGAAAA-3′ (SEQ ID NO: 1633) MYC-2332 21 ntTarget: 5′-UUUCUAUUGUUUUUAGAAAAA-3′ (SEQ ID NO: 1634) MYC-2333 21 ntTarget: 5′-UUCUAUUGUUUUUAGAAAAAA-3′ (SEQ ID NO: 1635)

TABLE 6 Selected Human Anti-MYC “Blunt/Fray” DsiRNAs

MYC-94 Target: 5′-CTCGAGAAGGGCAGGGCTTCTCAGAGG-3′ (SEQ ID NO: 655)

MYC-178 Target: 5′-GGGCTTTATCTAACTCGCTGTAGTAAT-3′ (SEQ ID NO: 656)

MYC-365 Target: 5′-AACCCTTGCCGCATCCACGAAACTTTG-3′ (SEQ ID NO: 657)

MYC-370 Target: 5′-TTGCCGCATCCACGAAACTTTGCCCAT-3′ (SEQ ID NO: 658)

MYC-376 Target: 5′-CATCCACGAAACTTTGCCCATAGCAGC-3′ (SEQ ID NO: 659)

MYC-403 Target: 5′-GGGCGGGCACTTTGCACTGGAACTTAC-3′ (SEQ ID NO: 660)

MYC-409 Target: 5′-GCACTTTGCACTGGAACTTACAACACC-3′ (SEQ ID NO: 661)

MYC-417 Target: 5′-CACTGGAACTTACAACACCCGAGCAAG-3′ (SEQ ID NO: 662)

MYC-535 Target: 5′-TTGCAGCTGCTTAGACGCTGGATTTTT-3′ (SEQ ID NO: 663)

MYC-541 Target: 5′-CTGCTTAGACGCTGGATTTTTTTCGGG-3′ (SEQ ID NO: 664)

MYC-548 Target: 5′-GACGCTGGATTTTTTTCGGGTAGTGGA-3′ (SEQ ID NO: 665)

MYC-553 Target: 5′-TGGATTTTTTTCGGGTAGTGGAAAACC-3′ (SEQ ID NO: 666)

MYC-562 Target: 5′-TTCGGGTAGTGGAAAACCAGCAGCCTC-3′ (SEQ ID NO: 667)

MYC-601 Target: 5′-CCCTCAACGTTAGCTTCACCAACAGGA-3′ (SEQ ID NO: 668)

MYC-607 Target: 5′-ACGTTAGCTTCACCAACAGGAACTATG-3′ (SEQ ID NO: 669)

MYC-643 Target: 5′-ACGACTCGGTGCAGCCGTATTTCTACT-3′ (SEQ ID NO: 670)

MYC-651 Target: 5′-GTGCAGCCGTATTTCTACTGCGACGAG-3′ (SEQ ID NO: 671)

MYC-676 Target: 5′-AGGAGGAGAACTTCTACCAGCAGCAGC-3′ (SEQ ID NO: 672)

MYC-731 Target: 5′-CAGCGAGGATATCTGGAAGAAATTCGA-3′ (SEQ ID NO: 673)

MYC-816 Target: 5′-TACGTTGCGGTCACACCCTTCTCCCTT-3′ (SEQ ID NO: 674)

MYC-920 Target: 5′-AGACATGGTGAACCAGAGTTTCATCTG-3′ (SEQ ID NO: 675)

MYC-949 Target: 5′-ACCCGGACGACGAGACCTTCATCAAAA-3′ (SEQ ID NO: 676)

MYC-958 Target: 5′-ACGAGACCTTCATCAAAAACATCATCA-3′ (SEQ ID NO: 677)

MYC-970 Target: 5′-TCAAAAACATCATCATCCAGGACTGTA-3′ (SEQ ID NO: 678)

MYC-987 Target: 5′-CAGGACTGTATGTGGAGCGGCTTCTCG-3′ (SEQ ID NO: 679)

MYC-1104 Target: 5′-GTCTGCTCCACCTCCAGCTTGTACCTG-3′ (SEQ ID NO: 680)

MYC-1111 Target: 5′-CCACCTCCAGCTTGTACCTGCAGGATC-3′ (SEQ ID NO: 681)

MYC-1116 Target: 5′-TCCAGCTTGTACCTGCAGGATCTGAGC-3′ (SEQ ID NO: 682)

MYC-1210 Target: 5′-CCAAGTCCTGCGCCTCGCAAGACTCCA-3′ (SEQ ID NO: 683)

MYC-1340 Target: 5′-CAGCAGCGACTCTGAGGAGGAACAAGA-3′ (SEQ ID NO: 684)

MYC-1346 Target: 5′-CGACTCTGAGGAGGAACAAGAAGATGA-3′ (SEQ ID NO: 685)

MYC-1351 Target: 5′-CTGAGGAGGAACAAGAAGATGAGGAAG-3′ (SEQ ID NO: 686)

MYC-1358 Target: 5′-GGAACAAGAAGATGAGGAAGAAATCGA-3′ (SEQ ID NO: 687)

MYC-1364 Target: 5′-AGAAGATGAGGAAGAAATCGATGTTGT-3′ (SEQ ID NO: 688)

MYC-1370 Target: 5′-TGAGGAAGAAATCGATGTTGTTTCTGT-3′ (SEQ ID NO: 689)

MYC-1376 Target: 5′-AGAAATCGATGTTGTTTCTGTGGAAAA-3′ (SEQ ID NO: 690)

MYC-1382 Target: 5′-CGATGTTGTTTCTGTGGAAAAGAGGCA-3′ (SEQ ID NO: 691)

MYC-1401 Target: 5′-AAGAGGCAGGCTCCTGGCAAAAGGTCA-3′ (SEQ ID NO: 692)

MYC-1406 Target: 5′-GCAGGCTCCTGGCAAAAGGTCAGAGTC-3′ (SEQ ID NO: 693)

MYC-1411 Target: 5′-CTCCTGGCAAAAGGTCAGAGTCTGGAT-3′ (SEQ ID NO: 694)

MYC-1416 Target: 5′-GGCAAAAGGTCAGAGTCTGGATCACCT-3′ (SEQ ID NO: 695)

MYC-1421 Target: 5′-AAGGTCAGAGTCTGGATCACCTTCTGC-3′ (SEQ ID NO: 696)

MYC-1457 Target: 5′-CAGCAAACCTCCTCACAGCCCACTGGT-3′ (SEQ ID NO: 697)

MYC-1465 Target: 5′-CTCCTCACAGCCCACTGGTCCTCAAGA-3′ (SEQ ID NO: 698)

MYC-1531 Target: 5′-CTCCCTCCACTCGGAAGGACTATCCTG-3′ (SEQ ID NO: 699)

MYC-1538 Target: 5′-CACTCGGAAGGACTATCCTGCTGCCAA-3′ (SEQ ID NO: 700)

MYC-1550 Target: 5′-CTATCCTGCTGCCAAGAGGGTCAAGTT-3′ (SEQ ID NO: 701)

MYC-1555 Target: 5′-CTGCTGCCAAGAGGGTCAAGTTGGACA-3′ (SEQ ID NO: 702)

MYC-1560 Target: 5′-GCCAAGAGGGTCAAGTTGGACAGTGTC-3′ (SEQ ID NO: 703)

MYC-1565 Target: 5′-GAGGGTCAAGTTGGACAGTGTCAGAGT-3′ (SEQ ID NO: 704)

MYC-1570 Target: 5′-TCAAGTTGGACAGTGTCAGAGTCCTGA-3′ (SEQ ID NO: 705)

MYC-1575 Target: 5′-TTGGACAGTGTCAGAGTCCTGAGACAG-3′ (SEQ ID NO: 706)

MYC-1584 Target: 5′-GTCAGAGTCCTGAGACAGATCAGCAAC-3′ (SEQ ID NO: 707)

MYC-1593 Target: 5′-CTGAGACAGATCAGCAACAACCGAAAA-3′ (SEQ ID NO: 708)

MYC-1599 Target: 5′-CAGATCAGCAACAACCGAAAATGCACC-3′ (SEQ ID NO: 709)

MYC-1634 Target: 5′-GTCCTCGGACACCGAGGAGAATGTCAA-3′ (SEQ ID NO: 710)

MYC-1639 Target: 5′-CGGACACCGAGGAGAATGTCAAGAGGC-3′ (SEQ ID NO: 711)

MYC-1687 Target: 5′-GCCAGAGGAGGAACGAGCTAAAACGGA-3′ (SEQ ID NO: 712)

MYC-1693 Target: 5′-GGAGGAACGAGCTAAAACGGAGCTTTT-3′ (SEQ ID NO: 713)

MYC-1698 Target: 5′-AACGAGCTAAAACGGAGCTTTTTTGCC-3′ (SEQ ID NO: 714)

MYC-1704 Target: 5′-CTAAAACGGAGCTTTTTTGCCCTGCGT-3′ (SEQ ID NO: 715)

MYC-1709 Target: 5′-ACGGAGCTTTTTTGCCCTGCGTGACCA-3′ (SEQ ID NO: 716)

MYC-1729 Target: 5′-GTGACCAGATCCCGGAGTTGGAAAACA-3′ (SEQ ID NO: 717)

MYC-1734 Target: 5′-CAGATCCCGGAGTTGGAAAACAATGAA-3′ (SEQ ID NO: 718)

MYC-1739 Target: 5′-CCCGGAGTTGGAAAACAATGAAAAGGC-3′ (SEQ ID NO: 719)

MYC-1769 Target: 5′-CAAGGTAGTTATCCTTAAAAAAGCCAC-3′ (SEQ ID NO: 720)

MYC-1774 Target: 5′-TAGTTATCCTTAAAAAAGCCACAGCAT-3′ (SEQ ID NO: 721)

MYC-1779 Target: 5′-ATCCTTAAAAAAGCCACAGCATACATC-3′ (SEQ ID NO: 722)

MYC-1784 Target: 5′-TAAAAAAGCCACAGCATACATCCTGTC-3′ (SEQ ID NO: 723)

MYC-1789 Target: 5′-AAGCCACAGCATACATCCTGTCCGTCC-3′ (SEQ ID NO: 724)

MYC-1795 Target: 5′-CAGCATACATCCTGTCCGTCCAAGCAG-3′ (SEQ ID NO: 725)

MYC-1803 Target: 5′-ATCCTGTCCGTCCAAGCAGAGGAGCAA-3′ (SEQ ID NO: 726)

MYC-1808 Target: 5′-GTCCGTCCAAGCAGAGGAGCAAAAGCT-3′ (SEQ ID NO: 727)

MYC-1816 Target: 5′-AAGCAGAGGAGCAAAAGCTCATTTCTG-3′ (SEQ ID NO: 728)

MYC-1823 Target: 5′-GGAGCAAAAGCTCATTTCTGAAGAGGA-3′ (SEQ ID NO: 729)

MYC-1828 Target: 5′-AAAAGCTCATTTCTGAAGAGGACTTGT-3′ (SEQ ID NO: 730)

MYC-1834 Target: 5′-TCATTTCTGAAGAGGACTTGTTGCGGA-3′ (SEQ ID NO: 731)

MYC-1840 Target: 5′-CTGAAGAGGACTTGTTGCGGAAACGAC-3′ (SEQ ID NO: 732)

MYC-1845 Target: 5′-GAGGACTTGTTGCGGAAACGACGAGAA-3′ (SEQ ID NO: 733)

MYC-1850 Target: 5′-CTTGTTGCGGAAACGACGAGAACAGTT-3′ (SEQ ID NO: 734)

MYC-1855 Target: 5′-TGCGGAAACGACGAGAACAGTTGAAAC-3′ (SEQ ID NO: 735)

MYC-1882 Target: 5′-ACAAACTTGAACAGCTACGGAACTCTT-3′ (SEQ ID NO: 736)

MYC-1888 Target: 5′-TTGAACAGCTACGGAACTCTTGTGCGT-3′ (SEQ ID NO: 737)

MYC-1893 Target: 5′-CAGCTACGGAACTCTTGTGCGTAAGGA-3′ (SEQ ID NO: 738)

MYC-1900 Target: 5′-GGAACTCTTGTGCGTAAGGAAAAGTAA-3′ (SEQ ID NO: 739)

MYC-1906 Target: 5′-CTTGTGCGTAAGGAAAAGTAAGGAAAA-3′ (SEQ ID NO: 740)

MYC-1911 Target: 5′-GCGTAAGGAAAAGTAAGGAAAACGATT-3′ (SEQ ID NO: 741)

MYC-1921 Target: 5′-AAGTAAGGAAAACGATTCCTTCTAACA-3′ (SEQ ID NO: 742)

MYC-1926 Target: 5′-AGGAAAACGATTCCTTCTAACAGAAAT-3′ (SEQ ID NO: 743)

MYC-1931 Target: 5′-AACGATTCCTTCTAACAGAAATGTCCT-3′ (SEQ ID NO: 744)

MYC-1937 Target: 5′-TCCTTCTAACAGAAATGTCCTGAGCAA-3′ (SEQ ID NO: 745)

MYC-1944 Target: 5′-AACAGAAATGTCCTGAGCAATCACCTA-3′ (SEQ ID NO: 746)

MYC-1953 Target: 5′-GTCCTGAGCAATCACCTATGAACTTGT-3′ (SEQ ID NO: 747)

MYC-1959 Target: 5′-AGCAATCACCTATGAACTTGTTTCAAA-3′ (SEQ ID NO: 748)

MYC-1965 Target: 5′-CACCTATGAACTTGTTTCAAATGCATG-3′ (SEQ ID NO: 749)

MYC-1970 Target: 5′-ATGAACTTGTTTCAAATGCATGATCAA-3′ (SEQ ID NO: 750)

MYC-1976 Target: 5′-TTGTTTCAAATGCATGATCAAATGCAA-3′ (SEQ ID NO: 751)

MYC-1981 Target: 5′-TCAAATGCATGATCAAATGCAACCTCA-3′ (SEQ ID NO: 752)

MYC-1989 Target: 5′-ATGATCAAATGCAACCTCACAACCTTG-3′ (SEQ ID NO: 753)

MYC-1994 Target: 5′-CAAATGCAACCTCACAACCTTGGCTGA-3′ (SEQ ID NO: 754)

MYC-2001 Target: 5′-AACCTCACAACCTTGGCTGAGTCTTGA-3′ (SEQ ID NO: 755)

MYC-2006 Target: 5′-CACAACCTTGGCTGAGTCTTGAGACTG-3′ (SEQ ID NO: 756)

MYC-2013 Target: 5′-TTGGCTGAGTCTTGAGACTGAAAGATT-3′ (SEQ ID NO: 757)

MYC-2019 Target: 5′-GAGTCTTGAGACTGAAAGATTTAGCCA-3′ (SEQ ID NO: 758)

MYC-2026 Target: 5′-GAGACTGAAAGATTTAGCCATAATGTA-3′ (SEQ ID NO: 759)

MYC-2031 Target: 5′-TGAAAGATTTAGCCATAATGTAAACTG-3′ (SEQ ID NO: 760)

MYC-2040 Target: 5′-TAGCCATAATGTAAACTGCCTCAAATT-3′ (SEQ ID NO: 761)

MYC-2048 Target: 5′-ATGTAAACTGCCTCAAATTGGACTTTG-3′ (SEQ ID NO: 762)

MYC-2054 Target: 5′-ACTGCCTCAAATTGGACTTTGGGCATA-3′ (SEQ ID NO: 763)

MYC-2059 Target: 5′-CTCAAATTGGACTTTGGGCATAAAAGA-3′ (SEQ ID NO: 764)

MYC-2066 Target: 5′-TGGACTTTGGGCATAAAAGAACTTTTT-3′ (SEQ ID NO: 765)

MYC-2073 Target: 5′-TGGGCATAAAAGAACTTTTTTATGCTT-3′ (SEQ ID NO: 766)

MYC-2078 Target: 5′-ATAAAAGAACTTTTTTATGCTTACCAT-3′ (SEQ ID NO: 767)

MYC-2083 Target: 5′-AGAACTTTTTTATGCTTACCATCTTTT-3′ (SEQ ID NO: 768)

MYC-2089 Target: 5′-TTTTTATGCTTACCATCTTTTTTTTTT-3′ (SEQ ID NO: 769)

MYC-2094 Target: 5′-ATGCTTACCATCTTTTTTTTTTCTTTA-3′ (SEQ ID NO: 770)

MYC-2099 Target: 5′-TACCATCTTTTTTTTTTCTTTAACAGA-3′ (SEQ ID NO: 771)

MYC-2105 Target: 5′-CTTTTTTTTTTCTTTAACAGATTTGTA-3′ (SEQ ID NO: 772)

MYC-2114 Target: 5′-TTCTTTAACAGATTTGTATTTAAGAAT-3′ (SEQ ID NO: 773)

MYC-2120 Target: 5′-AACAGATTTGTATTTAAGAATTGTTTT-3′ (SEQ ID NO: 774)

MYC-2128 Target: 5′-TGTATTTAAGAATTGTTTTTAAAAAAT-3′ (SEQ ID NO: 775)

MYC-2135 Target: 5′-AAGAATTGTTTTTAAAAAATTTTAAGA-3′ (SEQ ID NO: 776)

MYC-2167 Target: 5′-ACAATGTTTCTCTGTAAATATTGCCAT-3′ (SEQ ID NO: 777)

MYC-2176 Target: 5′-CTCTGTAAATATTGCCATTAAATGTAA-3′ (SEQ ID NO: 778)

MYC-2181 Target: 5′-TAAATATTGCCATTAAATGTAAATAAC-3′ (SEQ ID NO: 779)

MYC-2188 Target: 5′-TGCCATTAAATGTAAATAACTTTAATA-3′ (SEQ ID NO: 780)

MYC-2207 Target: 5′-CTTTAATAAAACGTTTATAGCAGTTAC-3′ (SEQ ID NO: 781)

MYC-2233 Target: 5′-CACAGAATTTCAATCCTAGTATATAGT-3′ (SEQ ID NO: 782)

MYC-2260 Target: 5′-ACCTAGTATTATAGGTACTATAAACCC-3′ (SEQ ID NO: 783)

MYC-2267 Target: 5′-ATTATAGGTACTATAAACCCTAATTTT-3′ (SEQ ID NO: 784)

MYC-2274 Target: 5′-GTACTATAAACCCTAATTTTTTTTATT-3′ (SEQ ID NO: 785)

MYC-2282 Target: 5′-AACCCTAATTTTTTTTATTTAAGTACA-3′ (SEQ ID NO: 786)

MYC-2287 Target: 5′-TAATTTTTTTTATTTAAGTACATTTTG-3′ (SEQ ID NO: 787)

MYC-2295 Target: 5′-TTTATTTAAGTACATTTTGCTTTTTAA-3′ (SEQ ID NO: 788)

MYC-2300 Target: 5′-TTAAGTACATTTTGCTTTTTAAAGTTG-3′ (SEQ ID NO: 789)

MYC-2306 Target: 5′-ACATTTTGCTTTTTAAAGTTGATTTTT-3′ (SEQ ID NO: 790)

MYC-2312 Target: 5′-TGCTTTTTAAAGTTGATTTTTTTCTAT-3′ (SEQ ID NO: 791)

MYC-2334 Target: 5′-TCTATTGTTTTTAGAAAAAATAAAATA-3′ (SEQ ID NO: 792)

MYC-2339 Target: 5′-TGTTTTTAGAAAAAATAAAATAACTGG-3′ (SEQ ID NO: 793)

MYC-2347 Target: 5′-GAAAAAATAAAATAACTGGCAAATATA-3′ (SEQ ID NO: 794)

MYC-2355 Target: 5′-AAAATAACTGGCAAATATATCATTGAG-3′ (SEQ ID NO: 795)

MYC-2364 Target: 5′-GGCAAATATATCATTGAGCCAAATCTT-3′ (SEQ ID NO: 796)

MYC-2371 Target: 5′-ATATCATTGAGCCAAATCTTAAAAAAA-3′ (SEQ ID NO: 797)

MYC-2377 Target: 5′-TTGAGCCAAATCTTAAAAAAAAAAAAA-3′ (SEQ ID NO: 798)

MYC-188 Target: 5′-TAACTCGCTGTAGTAATTCCAGCGAGA-3′ (SEQ ID NO: 799)

MYC-189 Target: 5′-AACTCGCTGTAGTAATTCCAGCGAGAG-3′ (SEQ ID NO: 800)

MYC-190 Target: 5′-ACTCGCTGTAGTAATTCCAGCGAGAGG-3′ (SEQ ID NO: 801)

MYC-191 Target: 5′-CTCGCTGTAGTAATTCCAGCGAGAGGC-3′ (SEQ ID NO: 802)

MYC-192 Target: 5′-TCGCTGTAGTAATTCCAGCGAGAGGCA-3′ (SEQ ID NO: 803)

MYC-193 Target: 5′-CGCTGTAGTAATTCCAGCGAGAGGCAG-3′ (SEQ ID NO: 804)

MYC-194 Target: 5′-GCTGTAGTAATTCCAGCGAGAGGCAGA-3′ (SEQ ID NO: 805)

MYC-195 Target: 5′-CTGTAGTAATTCCAGCGAGAGGCAGAG-3′ (SEQ ID NO: 806)

MYC-612 Target: 5′-AGCTTCACCAACAGGAACTATGACCTC-3′ (SEQ ID NO: 807)

MYC-613 Target: 5′-GCTTCACCAACAGGAACTATGACCTCG-3′ (SEQ ID NO: 808)

MYC-614 Target: 5′-CTTCACCAACAGGAACTATGACCTCGA-3′ (SEQ ID NO: 809)

MYC-615 Target: 5′-TTCACCAACAGGAACTATGACCTCGAC-3′ (SEQ ID NO: 810)

MYC-616 Target: 5′-TCACCAACAGGAACTATGACCTCGACT-3′ (SEQ ID NO: 811)

MYC-617 Target: 5′-CACCAACAGGAACTATGACCTCGACTA-3′ (SEQ ID NO: 812)

MYC-618 Target: 5′-ACCAACAGGAACTATGACCTCGACTAC-3′ (SEQ ID NO: 813)

MYC-619 Target: 5′-CCAACAGGAACTATGACCTCGACTACG-3′ (SEQ ID NO: 814)

MYC-620 Target: 5′-CAACAGGAACTATGACCTCGACTACGA-3′ (SEQ ID NO: 815)

MYC-621 Target: 5′-AACAGGAACTATGACCTCGACTACGAC-3′ (SEQ ID NO: 816)

MYC-622 Target: 5′-ACAGGAACTATGACCTCGACTACGACT-3′ (SEQ ID NO: 817)

MYC-623 Target: 5′-CAGGAACTATGACCTCGACTACGACTC-3′ (SEQ ID NO: 818)

MYC-624 Target: 5′-AGGAACTATGACCTCGACTACGACTCG-3′ (SEQ ID NO: 819)

MYC-625 Target: 5′-GGAACTATGACCTCGACTACGACTCGG-3′ (SEQ ID NO: 820)

MYC-626 Target: 5′-GAACTATGACCTCGACTACGACTCGGT-3′ (SEQ ID NO: 821)

MYC-627 Target: 5′-AACTATGACCTCGACTACGACTCGGTG-3′ (SEQ ID NO: 822)

MYC-628 Target: 5′-ACTATGACCTCGACTACGACTCGGTGC-3′ (SEQ ID NO: 823)

MYC-629 Target: 5′-CTATGACCTCGACTACGACTCGGTGCA-3′ (SEQ ID NO: 824)

MYC-733 Target: 5′-GCGAGGATATCTGGAAGAAATTCGAGC-3′ (SEQ ID NO: 825)

MYC-734 Target: 5′-CGAGGATATCTGGAAGAAATTCGAGCT-3′ (SEQ ID NO: 826)

MYC-735 Target: 5′-GAGGATATCTGGAAGAAATTCGAGCTG-3′ (SEQ ID NO: 827)

MYC-736 Target: 5′-AGGATATCTGGAAGAAATTCGAGCTGC-3′ (SEQ ID NO: 828)

MYC-737 Target: 5′-GGATATCTGGAAGAAATTCGAGCTGCT-3′ (SEQ ID NO: 829)

MYC-738 Target: 5′-GATATCTGGAAGAAATTCGAGCTGCTG-3′ (SEQ ID NO: 830)

MYC-739 Target: 5′-ATATCTGGAAGAAATTCGAGCTGCTGC-3′ (SEQ ID NO: 831)

MYC-740 Target: 5′-TATCTGGAAGAAATTCGAGCTGCTGCC-3′ (SEQ ID NO: 832)

MYC-741 Target: 5′-ATCTGGAAGAAATTCGAGCTGCTGCCC-3′ (SEQ ID NO: 833)

MYC-742 Target: 5′-TCTGGAAGAAATTCGAGCTGCTGCCCA-3′ (SEQ ID NO: 834)

MYC-743 Target: 5′-CTGGAAGAAATTCGAGCTGCTGCCCAC-3′ (SEQ ID NO: 835)

MYC-784 Target: 5′-CTAGCCGCCGCTCCGGGCTCTGCTCGC-3′ (SEQ ID NO: 836)

MYC-785 Target: 5′-TAGCCGCCGCTCCGGGCTCTGCTCGCC-3′ (SEQ ID NO: 837)

MYC-786 Target: 5′-AGCCGCCGCTCCGGGCTCTGCTCGCCC-3′ (SEQ ID NO: 838)

MYC-787 Target: 5′-GCCGCCGCTCCGGGCTCTGCTCGCCCT-3′ (SEQ ID NO: 839)

MYC-788 Target: 5′-CCGCCGCTCCGGGCTCTGCTCGCCCTC-3′ (SEQ ID NO: 840)

MYC-913 Target: 5′-TGGGAGGAGACATGGTGAACCAGAGTT-3′ (SEQ ID NO: 841)

MYC-914 Target: 5′-GGGAGGAGACATGGTGAACCAGAGTTT-3′ (SEQ ID NO: 842)

MYC-915 Target: 5′-GGAGGAGACATGGTGAACCAGAGTTTC-3′ (SEQ ID NO: 843)

MYC-916 Target: 5′-GAGGAGACATGGTGAACCAGAGTTTCA-3′ (SEQ ID NO: 844)

MYC-917 Target: 5′-AGGAGACATGGTGAACCAGAGTTTCAT-3′ (SEQ ID NO: 845)

MYC-952 Target: 5′-CGGACGACGAGACCTTCATCAAAAACA-3′ (SEQ ID NO: 846)

MYC-953 Target: 5′-GGACGACGAGACCTTCATCAAAAACAT-3′ (SEQ ID NO: 847)

MYC-973 Target: 5′-AAAACATCATCATCCAGGACTGTATGT-3′ (SEQ ID NO: 848)

MYC-974 Target: 5′-AAACATCATCATCCAGGACTGTATGTG-3′ (SEQ ID NO: 849)

MYC-975 Target: 5′-AACATCATCATCCAGGACTGTATGTGG-3′ (SEQ ID NO: 850)

MYC-976 Target: 5′-ACATCATCATCCAGGACTGTATGTGGA-3′ (SEQ ID NO: 851)

MYC-977 Target: 5′-CATCATCATCCAGGACTGTATGTGGAG-3′ (SEQ ID NO: 852)

MYC-978 Target: 5′-ATCATCATCCAGGACTGTATGTGGAGC-3′ (SEQ ID NO: 853)

MYC-979 Target: 5′-TCATCATCCAGGACTGTATGTGGAGCG-3′ (SEQ ID NO: 854)

MYC-980 Target: 5′-CATCATCCAGGACTGTATGTGGAGCGG-3′ (SEQ ID NO: 855)

MYC-981 Target: 5′-ATCATCCAGGACTGTATGTGGAGCGGC-3′ (SEQ ID NO: 856)

MYC-982 Target: 5′-TCATCCAGGACTGTATGTGGAGCGGCT-3′ (SEQ ID NO: 857)

MYC-983 Target: 5′-CATCCAGGACTGTATGTGGAGCGGCTT-3′ (SEQ ID NO: 858)

MYC-984 Target: 5′-ATCCAGGACTGTATGTGGAGCGGCTTC-3′ (SEQ ID NO: 859)

MYC-985 Target: 5′-TCCAGGACTGTATGTGGAGCGGCTTCT-3′ (SEQ ID NO: 860)

MYC-986 Target: 5′-CCAGGACTGTATGTGGAGCGGCTTCTC-3′ (SEQ ID NO: 861)

MYC-1033 Target: 5′-CAGAGAAGCTGGCCTCCTACCAGGCTG-3′ (SEQ ID NO: 862)

MYC-1034 Target: 5′-AGAGAAGCTGGCCTCCTACCAGGCTGC-3′ (SEQ ID NO: 863)

MYC-1035 Target: 5′-GAGAAGCTGGCCTCCTACCAGGCTGCG-3′ (SEQ ID NO: 864)

MYC-1036 Target: 5′-AGAAGCTGGCCTCCTACCAGGCTGCGC-3′ (SEQ ID NO: 865)

MYC-1037 Target: 5′-GAAGCTGGCCTCCTACCAGGCTGCGCG-3′ (SEQ ID NO: 866)

MYC-1038 Target: 5′-AAGCTGGCCTCCTACCAGGCTGCGCGC-3′ (SEQ ID NO: 867)

MYC-1039 Target: 5′-AGCTGGCCTCCTACCAGGCTGCGCGCA-3′ (SEQ ID NO: 868)

MYC-1040 Target: 5′-GCTGGCCTCCTACCAGGCTGCGCGCAA-3′ (SEQ ID NO: 869)

MYC-1041 Target: 5′-CTGGCCTCCTACCAGGCTGCGCGCAAA-3′ (SEQ ID NO: 870)

MYC-1042 Target: 5′-TGGCCTCCTACCAGGCTGCGCGCAAAG-3′ (SEQ ID NO: 871)

MYC-1043 Target: 5′-GGCCTCCTACCAGGCTGCGCGCAAAGA-3′ (SEQ ID NO: 872)

MYC-1044 Target: 5′-GCCTCCTACCAGGCTGCGCGCAAAGAC-3′ (SEQ ID NO: 873)

MYC-1045 Target: 5′-CCTCCTACCAGGCTGCGCGCAAAGACA-3′ (SEQ ID NO: 874)

MYC-1046 Target: 5′-CTCCTACCAGGCTGCGCGCAAAGACAG-3′ (SEQ ID NO: 875)

MYC-1047 Target: 5′-TCCTACCAGGCTGCGCGCAAAGACAGC-3′ (SEQ ID NO: 876)

MYC-1048 Target: 5′-CCTACCAGGCTGCGCGCAAAGACAGCG-3′ (SEQ ID NO: 877)

MYC-1049 Target: 5′-CTACCAGGCTGCGCGCAAAGACAGCGG-3′ (SEQ ID NO: 878)

MYC-1050 Target: 5′-TACCAGGCTGCGCGCAAAGACAGCGGC-3′ (SEQ ID NO: 879)

MYC-1051 Target: 5′-ACCAGGCTGCGCGCAAAGACAGCGGCA-3′ (SEQ ID NO: 880)

MYC-1052 Target: 5′-CCAGGCTGCGCGCAAAGACAGCGGCAG-3′ (SEQ ID NO: 881)

MYC-1053 Target: 5′-CAGGCTGCGCGCAAAGACAGCGGCAGC-3′ (SEQ ID NO: 882)

MYC-1096 Target: 5′-GCCACAGCGTCTGCTCCACCTCCAGCT-3′ (SEQ ID NO: 883)

MYC-1097 Target: 5′-CCACAGCGTCTGCTCCACCTCCAGCTT-3′ (SEQ ID NO: 884)

MYC-1098 Target: 5′-CACAGCGTCTGCTCCACCTCCAGCTTG-3′ (SEQ ID NO: 885)

MYC-1099 Target: 5′-ACAGCGTCTGCTCCACCTCCAGCTTGT-3′ (SEQ ID NO: 886)

MYC-1100 Target: 5′-CAGCGTCTGCTCCACCTCCAGCTTGTA-3′ (SEQ ID NO: 887)

MYC-1101 Target: 5′-AGCGTCTGCTCCACCTCCAGCTTGTAC-3′ (SEQ ID NO: 888)

MYC-1189 Target: 5′-CTCTCAACGACAGCAGCTCGCCCAAGT-3′ (SEQ ID NO: 889)

MYC-1190 Target: 5′-TCTCAACGACAGCAGCTCGCCCAAGTC-3′ (SEQ ID NO: 890)

MYC-1191 Target: 5′-CTCAACGACAGCAGCTCGCCCAAGTCC-3′ (SEQ ID NO: 891)

MYC-1192 Target: 5′-TCAACGACAGCAGCTCGCCCAAGTCCT-3′ (SEQ ID NO: 892)

MYC-1193 Target: 5′-CAACGACAGCAGCTCGCCCAAGTCCTG-3′ (SEQ ID NO: 893)

MYC-1315 Target: 5′-TCCATGAGGAGACACCGCCCACCACCA-3′ (SEQ ID NO: 894)

MYC-1316 Target: 5′-CCATGAGGAGACACCGCCCACCACCAG-3′ (SEQ ID NO: 895)

MYC-1317 Target: 5′-CATGAGGAGACACCGCCCACCACCAGC-3′ (SEQ ID NO: 896)

MYC-1318 Target: 5′-ATGAGGAGACACCGCCCACCACCAGCA-3′ (SEQ ID NO: 897)

MYC-1319 Target: 5′-TGAGGAGACACCGCCCACCACCAGCAG-3′ (SEQ ID NO: 898)

MYC-1320 Target: 5′-GAGGAGACACCGCCCACCACCAGCAGC-3′ (SEQ ID NO: 899)

MYC-1321 Target: 5′-AGGAGACACCGCCCACCACCAGCAGCG-3′ (SEQ ID NO: 900)

MYC-1322 Target: 5′-GGAGACACCGCCCACCACCAGCAGCGA-3′ (SEQ ID NO: 901)

MYC-1323 Target: 5′-GAGACACCGCCCACCACCAGCAGCGAC-3′ (SEQ ID NO: 902)

MYC-1324 Target: 5′-AGACACCGCCCACCACCAGCAGCGACT-3′ (SEQ ID NO: 903)

MYC-1325 Target: 5′-GACACCGCCCACCACCAGCAGCGACTC-3′ (SEQ ID NO: 904)

MYC-1326 Target: 5′-ACACCGCCCACCACCAGCAGCGACTCT-3′ (SEQ ID NO: 905)

MYC-1327 Target: 5′-CACCGCCCACCACCAGCAGCGACTCTG-3′ (SEQ ID NO: 906)

MYC-1328 Target: 5′-ACCGCCCACCACCAGCAGCGACTCTGA-3′ (SEQ ID NO: 907)

MYC-1329 Target: 5′-CCGCCCACCACCAGCAGCGACTCTGAG-3′ (SEQ ID NO: 908)

MYC-1330 Target: 5′-CGCCCACCACCAGCAGCGACTCTGAGG-3′ (SEQ ID NO: 909)

MYC-1331 Target: 5′-GCCCACCACCAGCAGCGACTCTGAGGA-3′ (SEQ ID NO: 910)

MYC-1332 Target: 5′-CCCACCACCAGCAGCGACTCTGAGGAG-3′ (SEQ ID NO: 911)

MYC-1333 Target: 5′-CCACCACCAGCAGCGACTCTGAGGAGG-3′ (SEQ ID NO: 912)

MYC-1334 Target: 5′-CACCACCAGCAGCGACTCTGAGGAGGA-3′ (SEQ ID NO: 913)

MYC-1360 Target: 5′-AACAAGAAGATGAGGAAGAAATCGATG-3′ (SEQ ID NO: 914)

MYC-1361 Target: 5′-ACAAGAAGATGAGGAAGAAATCGATGT-3′ (SEQ ID NO: 915)

MYC-1448 Target: 5′-TGGAGGCCACAGCAAACCTCCTCACAG-3′ (SEQ ID NO: 916)

MYC-1468 Target: 5′-CTCACAGCCCACTGGTCCTCAAGAGGT-3′ (SEQ ID NO: 917)

MYC-1469 Target: 5′-TCACAGCCCACTGGTCCTCAAGAGGTG-3′ (SEQ ID NO: 918)

MYC-1470 Target: 5′-CACAGCCCACTGGTCCTCAAGAGGTGC-3′ (SEQ ID NO: 919)

MYC-1471 Target: 5′-ACAGCCCACTGGTCCTCAAGAGGTGCC-3′ (SEQ ID NO: 920)

MYC-1472 Target: 5′-CAGCCCACTGGTCCTCAAGAGGTGCCA-3′ (SEQ ID NO: 921)

MYC-1473 Target: 5′-AGCCCACTGGTCCTCAAGAGGTGCCAC-3′ (SEQ ID NO: 922)

MYC-1474 Target: 5′-GCCCACTGGTCCTCAAGAGGTGCCACG-3′ (SEQ ID NO: 923)

MYC-1475 Target: 5′-CCCACTGGTCCTCAAGAGGTGCCACGT-3′ (SEQ ID NO: 924)

MYC-1476 Target: 5′-CCACTGGTCCTCAAGAGGTGCCACGTC-3′ (SEQ ID NO: 925)

MYC-1477 Target: 5′-CACTGGTCCTCAAGAGGTGCCACGTCT-3′ (SEQ ID NO: 926)

MYC-1478 Target: 5′-ACTGGTCCTCAAGAGGTGCCACGTCTC-3′ (SEQ ID NO: 927)

MYC-1479 Target: 5′-CTGGTCCTCAAGAGGTGCCACGTCTCC-3′ (SEQ ID NO: 928)

MYC-1480 Target: 5′-TGGTCCTCAAGAGGTGCCACGTCTCCA-3′ (SEQ ID NO: 929)

MYC-1481 Target: 5′-GGTCCTCAAGAGGTGCCACGTCTCCAC-3′ (SEQ ID NO: 930)

MYC-1482 Target: 5′-GTCCTCAAGAGGTGCCACGTCTCCACA-3′ (SEQ ID NO: 931)

MYC-1483 Target: 5′-TCCTCAAGAGGTGCCACGTCTCCACAC-3′ (SEQ ID NO: 932)

MYC-1711 Target: 5′-GGAGCTTTTTTGCCCTGCGTGACCAGA-3′ (SEQ ID NO: 933)

MYC-1712 Target: 5′-GAGCTTTTTTGCCCTGCGTGACCAGAT-3′ (SEQ ID NO: 934)

MYC-1713 Target: 5′-AGCTTTTTTGCCCTGCGTGACCAGATC-3′ (SEQ ID NO: 935)

MYC-1714 Target: 5′-GCTTTTTTGCCCTGCGTGACCAGATCC-3′ (SEQ ID NO: 936)

MYC-1715 Target: 5′-CTTTTTTGCCCTGCGTGACCAGATCCC-3′ (SEQ ID NO: 937)

MYC-1716 Target: 5′-TTTTTTGCCCTGCGTGACCAGATCCCG-3′ (SEQ ID NO: 938)

MYC-1717 Target: 5′-TTTTTGCCCTGCGTGACCAGATCCCGG-3′ (SEQ ID NO: 939)

MYC-1718 Target: 5′-TTTTGCCCTGCGTGACCAGATCCCGGA-3′ (SEQ ID NO: 940)

MYC-1719 Target: 5′-TTTGCCCTGCGTGACCAGATCCCGGAG-3′ (SEQ ID NO: 941)

MYC-1720 Target: 5′-TTGCCCTGCGTGACCAGATCCCGGAGT-3′ (SEQ ID NO: 942)

MYC-1721 Target: 5′-TGCCCTGCGTGACCAGATCCCGGAGTT-3′ (SEQ ID NO: 943)

MYC-1856 Target: 5′-GCGGAAACGACGAGAACAGTTGAAACA-3′ (SEQ ID NO: 944)

MYC-1857 Target: 5′-CGGAAACGACGAGAACAGTTGAAACAC-3′ (SEQ ID NO: 945)

MYC-2115 Target: 5′-TCTTTAACAGATTTGTATTTAAGAATT-3′ (SEQ ID NO: 946)

MYC-2116 Target: 5′-CTTTAACAGATTTGTATTTAAGAATTG-3′ (SEQ ID NO: 947)

MYC-2193 Target: 5′-TTAAATGTAAATAACTTTAATAAAACG-3′ (SEQ ID NO: 948)

MYC-2194 Target: 5′-TAAATGTAAATAACTTTAATAAAACGT-3′ (SEQ ID NO: 949)

MYC-2195 Target: 5′-AAATGTAAATAACTTTAATAAAACGTT-3′ (SEQ ID NO: 950)

MYC-2196 Target: 5′-AATGTAAATAACTTTAATAAAACGTTT-3′ (SEQ ID NO: 951)

MYC-2197 Target: 5′-ATGTAAATAACTTTAATAAAACGTTTA-3′ (SEQ ID NO: 952)

MYC-2198 Target: 5′-TGTAAATAACTTTAATAAAACGTTTAT-3′ (SEQ ID NO: 953)

MYC-2199 Target: 5′-GTAAATAACTTTAATAAAACGTTTATA-3′ (SEQ ID NO: 954)

MYC-2200 Target: 5′-TAAATAACTTTAATAAAACGTTTATAG-3′ (SEQ ID NO: 955)

MYC-2201 Target: 5′-AAATAACTTTAATAAAACGTTTATAGC-3′ (SEQ ID NO: 956)

MYC-2202 Target: 5′-AATAACTTTAATAAAACGTTTATAGCA-3′ (SEQ ID NO: 957)

MYC-2203 Target: 5′-ATAACTTTAATAAAACGTTTATAGCAG-3′ (SEQ ID NO: 958)

MYC-2204 Target: 5′-TAACTTTAATAAAACGTTTATAGCAGT-3′ (SEQ ID NO: 959)

MYC-2205 Target: 5′-AACTTTAATAAAACGTTTATAGCAGTT-3′ (SEQ ID NO: 960)

MYC-2313 Target: 5′-GCTTTTTAAAGTTGATTTTTTTCTATT-3′ (SEQ ID NO: 961)

MYC-2314 Target: 5′-CTTTTTAAAGTTGATTTTTTTCTATTG-3′ (SEQ ID NO: 962)

MYC-2315 Target: 5′-TTTTTAAAGTTGATTTTTTTCTATTGT-3′ (SEQ ID NO: 963)

MYC-2316 Target: 5′-TTTTAAAGTTGATTTTTTTCTATTGTT-3′ (SEQ ID NO: 964)

MYC-2317 Target: 5′-TTTAAAGTTGATTTTTTTCTATTGTTT-3′ (SEQ ID NO: 965)

MYC-2318 Target: 5′-TTAAAGTTGATTTTTTTCTATTGTTTT-3′ (SEQ ID NO: 966)

MYC-2319 Target: 5′-TAAAGTTGATTTTTTTCTATTGTTTTT-3′ (SEQ ID NO: 967)

MYC-2320 Target: 5′-AAAGTTGATTTTTTTCTATTGTTTTTA-3′ (SEQ ID NO: 968)

MYC-2321 Target: 5′-AAGTTGATTTTTTTCTATTGTTTTTAG-3′ (SEQ ID NO: 969)

MYC-2322 Target: 5′-AGTTGATTTTTTTCTATTGTTTTTAGA-3′ (SEQ ID NO: 970)

MYC-2323 Target: 5′-GTTGATTTTTTTCTATTGTTTTTAGAA-3′ (SEQ ID NO: 971)

MYC-2324 Target: 5′-TTGATTTTTTTCTATTGTTTTTAGAAA-3′ (SEQ ID NO: 972)

MYC-2325 Target: 5′-TGATTTTTTTCTATTGTTTTTAGAAAA-3′ (SEQ ID NO: 973)

MYC-2326 Target: 5′-GATTTTTTTCTATTGTTTTTAGAAAAA-3′ (SEQ ID NO: 974)

MYC-2327 Target: 5′-ATTTTTTTCTATTGTTTTTAGAAAAAA-3′ (SEQ ID NO: 975)

MYC-2328 Target: 5′-TTTTTTTCTATTGTTTTTAGAAAAAAT-3′ (SEQ ID NO: 976)

MYC-2329 Target: 5′-TTTTTTCTATTGTTTTTAGAAAAAATA-3′ (SEQ ID NO: 977)

MYC-2330 Target: 5′-TTTTTCTATTGTTTTTAGAAAAAATAA-3′ (SEQ ID NO: 978)

MYC-2331 Target: 5′-TTTTCTATTGTTTTTAGAAAAAATAAA-3′ (SEQ ID NO: 979)

MYC-2332 Target: 5′-TTTCTATTGTTTTTAGAAAAAATAAAA-3′ (SEQ ID NO: 980)

MYC-2333 Target: 5′-TTCTATTGTTTTTAGAAAAAATAAAAT-3′ (SEQ ID NO: 981)

TABLE 7 Selected Human Anti-MYC “Blunt/Blunt” DsiRNAs5′-CUCGAGAAGGGCAGGGCUUCUCAGAGG-3′ (SEQ ID NO: 1963)3′-GAGCUCUUCCCGUCCCGAAGAGUCUCC-5′ (SEQ ID NO: 328) MYC-94 Target:5′-CTCGAGAAGGGCAGGGCTTCTCAGAGG-3′ (SEQ ID NO: 655)5′-GGGCUUUAUCUAACUCGCUGUAGUAAU-3′ (SEQ ID NO: 1964)3′-CCCGAAAUAGAUUGAGCGACAUCAUUA-5′ (SEQ ID NO: 329) MYC-178 Target:5′-GGGCTTTATCTAACTCGCTGTAGTAAT-3′ (SEQ ID NO: 656)5′-AACCCUUGCCGCAUCCACGAAACUUUG-3′ (SEQ ID NO: 1965)3′-UUGGGAACGGCGUAGGUGCUUUGAAAC-5′ (SEQ ID NO: 330) MYC-365 Target:5′-AACCCTTGCCGCATCCACGAAACTTTG-3′ (SEQ ID NO: 657)5′-UUGCCGCAUCCACGAAACUUUGCCCAU-3′ (SEQ ID NO: 1966)3′-AACGGCGUAGGUGCUUUGAAACGGGUA-5′ (SEQ ID NO: 331) MYC-370 Target:5′-TTGCCGCATCCACGAAACTTTGCCCAT-3′ (SEQ ID NO: 658)5′-CAUCCACGAAACUUUGCCCAUAGCAGC-3′ (SEQ ID NO: 1967)3′-GUAGGUGCUUUGAAACGGGUAUCGUCG-5′ (SEQ ID NO: 332) MYC-376 Target:5′-CATCCACGAAACTTTGCCCATAGCAGC-3′ (SEQ ID NO: 659)5′-GGGCGGGCACUUUGCACUGGAACUUAC-3′ (SEQ ID NO: 1968)3′-CCCGCCCGUGAAACGUGACCUUGAAUG-5′ (SEQ ID NO: 333) MYC-403 Target:5′-GGGCGGGCACTTTGCACTGGAACTTAC-3′ (SEQ ID NO: 660)5′-GCACUUUGCACUGGAACUUACAACACC-3′ (SEQ ID NO: 1969)3′-CGUGAAACGUGACCUUGAAUGUUGUGG-5′ (SEQ ID NO: 334) MYC-409 Target:5′-GCACTTTGCACTGGAACTTACAACACC-3′ (SEQ ID NO: 661)5′-CACUGGAACUUACAACACCCGAGCAAG-3′ (SEQ ID NO: 1970)3′-GUGACCUUGAAUGUUGUGGGCUCGUUC-5′ (SEQ ID NO: 335) MYC-417 Target:5′-CACTGGAACTTACAACACCCGAGCAAG-3′ (SEQ ID NO: 662)5′-UUGCAGCUGCUUAGACGCUGGAUUUUU-3′ (SEQ ID NO: 1971)3′-AACGUCGACGAAUCUGCGACCUAAAAA-5′ (SEQ ID NO: 336) MYC-535 Target:5′-TTGCAGCTGCTTAGACGCTGGATTTTT-3′ (SEQ ID NO: 663)5′-CUGCUUAGACGCUGGAUUUUUUUCGGG-3′ (SEQ ID NO: 1972)3′-GACGAAUCUGCGACCUAAAAAAAGCCC-5′ (SEQ ID NO: 337) MYC-541 Target:5′-CTGCTTAGACGCTGGATTTTTTTCGGG-3′ (SEQ ID NO: 664)5′-GACGCUGGAUUUUUUUCGGGUAGUGGA-3′ (SEQ ID NO: 1973)3′-CUGCGACCUAAAAAAAGCCCAUCACCU-5′ (SEQ ID NO: 338) MYC-548 Target:5′-GACGCTGGATTTTTTTCGGGTAGTGGA-3′ (SEQ ID NO: 665)5′-UGGAUUUUUUUCGGGUAGUGGAAAACC-3′ (SEQ ID NO: 1974)3′-ACCUAAAAAAAGCCCAUCACCUUUUGG-5′ (SEQ ID NO: 339) MYC-553 Target:5′-TGGATTTTTTTCGGGTAGTGGAAAACC-3′ (SEQ ID NO: 666)5′-UUCGGGUAGUGGAAAACCAGCAGCCUC-3′ (SEQ ID NO: 1975)3′-AAGCCCAUCACCUUUUGGUCGUCGGAG-5′ (SEQ ID NO: 340) MYC-562 Target:5′-TTCGGGTAGTGGAAAACCAGCAGCCTC-3′ (SEQ ID NO: 667)5′-CCCUCAACGUUAGCUUCACCAACAGGA-3′ (SEQ ID NO: 1976)3′-GGGAGUUGCAAUCGAAGUGGUUGUCCU-5′ (SEQ ID NO: 341) MYC-601 Target:5′-CCCTCAACGTTAGCTTCACCAACAGGA-3′ (SEQ ID NO: 668)5′-ACGUUAGCUUCACCAACAGGAACUAUG-3′ (SEQ ID NO: 1977)3′-UGCAAUCGAAGUGGUUGUCCUUGAUAC-5′ (SEQ ID NO: 342) MYC-607 Target:5′-ACGTTAGCTTCACCAACAGGAACTATG-3′ (SEQ ID NO: 669)5′-ACGACUCGGUGCAGCCGUAUUUCUACU-3′ (SEQ ID NO: 1978)3′-UGCUGAGCCACGUCGGCAUAAAGAUGA-5′ (SEQ ID NO: 343) MYC-643 Target:5′-ACGACTCGGTGCAGCCGTATTTCTACT-3′ (SEQ ID NO: 670)5′-GUGCAGCCGUAUUUCUACUGCGACGAG-3′ (SEQ ID NO: 1979)3′-CACGUCGGCAUAAAGAUGACGCUGCUC-5′ (SEQ ID NO: 344) MYC-651 Target:5′-GTGCAGCCGTATTTCTACTGCGACGAG-3′ (SEQ ID NO: 671)5′-AGGAGGAGAACUUCUACCAGCAGCAGC-3′ (SEQ ID NO: 1980)3′-UCCUCCUCUUGAAGAUGGUCGUCGUCG-5′ (SEQ ID NO: 345) MYC-676 Target:5′-AGGAGGAGAACTTCTACCAGCAGCAGC-3′ (SEQ ID NO: 672)5′-CAGCGAGGAUAUCUGGAAGAAAUUCGA-3′ (SEQ ID NO: 1981)3′-GUCGCUCCUAUAGACCUUCUUUAAGCU-5′ (SEQ ID NO: 346) MYC-731 Target:5′-CAGCGAGGATATCTGGAAGAAATTCGA-3′ (SEQ ID NO: 673)5′-UACGUUGCGGUCACACCCUUCUCCCUU-3′ (SEQ ID NO: 1982)3′-AUGCAACGCCAGUGUGGGAAGAGGGAA-5′ (SEQ ID NO: 347) MYC-816 Target:5′-TACGTTGCGGTCACACCCTTCTCCCTT-3′ (SEQ ID NO: 674)5′-AGACAUGGUGAACCAGAGUUUCAUCUG-3′ (SEQ ID NO: 1983)3′-UCUGUACCACUUGGUCUCAAAGUAGAC-5′ (SEQ ID NO: 348) MYC-920 Target:5′-AGACATGGTGAACCAGAGTTTCATCTG-3′ (SEQ ID NO: 675)5′-ACCCGGACGACGAGACCUUCAUCAAAA-3′ (SEQ ID NO: 1984)3′-UGGGCCUGCUGCUCUGGAAGUAGUUUU-5′ (SEQ ID NO: 349) MYC-949 Target:5′-ACCCGGACGACGAGACCTTCATCAAAA-3′ (SEQ ID NO: 676)5′-ACGAGACCUUCAUCAAAAACAUCAUCA-3′ (SEQ ID NO: 1985)3′-UGCUCUGGAAGUAGUUUUUGUAGUAGU-5′ (SEQ ID NO: 350) MYC-958 Target:5′-ACGAGACCTTCATCAAAAACATCATCA-3′ (SEQ ID NO: 677)5′-UCAAAAACAUCAUCAUCCAGGACUGUA-3′ (SEQ ID NO: 1986)3′-AGUUUUUGUAGUAGUAGGUCCUGACAU-5′ (SEQ ID NO: 351) MYC-970 Target:5′-TCAAAAACATCATCATCCAGGACTGTA-3′ (SEQ ID NO: 678)5′-CAGGACUGUAUGUGGAGCGGCUUCUCG-3′ (SEQ ID NO: 1987)3′-GUCCUGACAUACACCUCGCCGAAGAGC-5′ (SEQ ID NO: 352) MYC-987 Target:5′-CAGGACTGTATGTGGAGCGGCTTCTCG-3′ (SEQ ID NO: 679)5′-GUCUGCUCCACCUCCAGCUUGUACCUG-3′ (SEQ ID NO: 1988)3′-CAGACGAGGUGGAGGUCGAACAUGGAC-5′ (SEQ ID NO: 353) MYC-1104 Target:5′-GTCTGCTCCACCTCCAGCTTGTACCTG-3′ (SEQ ID NO: 680)5′-CCACCUCCAGCUUGUACCUGCAGGAUC-3′ (SEQ ID NO: 1989)3′-GGUGGAGGUCGAACAUGGACGUCCUAG-5′ (SEQ ID NO: 354) MYC-1111 Target:5′-CCACCTCCAGCTTGTACCTGCAGGATC-3′ (SEQ ID NO: 681)5′-UCCAGCUUGUACCUGCAGGAUCUGAGC-3′ (SEQ ID NO: 1990)3′-AGGUCGAACAUGGACGUCCUAGACUCG-5′ (SEQ ID NO: 355) MYC-1116 Target:5′-TCCAGCTTGTACCTGCAGGATCTGAGC-3′ (SEQ ID NO: 682)5′-CCAAGUCCUGCGCCUCGCAAGACUCCA-3′ (SEQ ID NO: 1991)3′-GGUUCAGGACGCGGAGCGUUCUGAGGU-5′ (SEQ ID NO: 356) MYC-1210 Target:5′-CCAAGTCCTGCGCCTCGCAAGACTCCA-3′ (SEQ ID NO: 683)5′-CAGCAGCGACUCUGAGGAGGAACAAGA-3′ (SEQ ID NO: 1992)3′-GUCGUCGCUGAGACUCCUCCUUGUUCU-5′ (SEQ ID NO: 357) MYC-1340 Target:5′-CAGCAGCGACTCTGAGGAGGAACAAGA-3′ (SEQ ID NO: 684)5′-CGACUCUGAGGAGGAACAAGAAGAUGA-3′ (SEQ ID NO: 1993)3′-GCUGAGACUCCUCCUUGUUCUUCUACU-5′ (SEQ ID NO: 358) MYC-1346 Target:5′-CGACTCTGAGGAGGAACAAGAAGATGA-3′ (SEQ ID NO: 685)5′-CUGAGGAGGAACAAGAAGAUGAGGAAG-3′ (SEQ ID NO: 1994)3′-GACUCCUCCUUGUUCUUCUACUCCUUC-5′ (SEQ ID NO: 359) MYC-1351 Target:5′-CTGAGGAGGAACAAGAAGATGAGGAAG-3′ (SEQ ID NO: 686)5′-GGAACAAGAAGAUGAGGAAGAAAUCGA-3′ (SEQ ID NO: 1995)3′-CCUUGUUCUUCUACUCCUUCUUUAGCU-5′ (SEQ ID NO: 360) MYC-1358 Target:5′-GGAACAAGAAGATGAGGAAGAAATCGA-3′ (SEQ ID NO: 687)5′-AGAAGAUGAGGAAGAAAUCGAUGUUGU-3′ (SEQ ID NO: 1996)3′-UCUUCUACUCCUUCUUUAGCUACAACA-5′ (SEQ ID NO: 361) MYC-1364 Target:5′-AGAAGATGAGGAAGAAATCGATGTTGT-3′ (SEQ ID NO: 688)5′-UGAGGAAGAAAUCGAUGUUGUUUCUGU-3′ (SEQ ID NO: 1997)3′-ACUCCUUCUUUAGCUACAACAAAGACA-5′ (SEQ ID NO: 362) MYC-1370 Target:5′-TGAGGAAGAAATCGATGTTGTTTCTGT-3′ (SEQ ID NO: 689)5′-AGAAAUCGAUGUUGUUUCUGUGGAAAA-3′ (SEQ ID NO: 1998)3′-UCUUUAGCUACAACAAAGACACCUUUU-5′ (SEQ ID NO: 363) MYC-1376 Target:5′-AGAAATCGATGTTGTTTCTGTGGAAAA-3′ (SEQ ID NO: 690)5′-CGAUGUUGUUUCUGUGGAAAAGAGGCA-3′ (SEQ ID NO: 1999)3′-GCUACAACAAAGACACCUUUUCUCCGU-5′ (SEQ ID NO: 364) MYC-1382 Target:5′-CGATGTTGTTTCTGTGGAAAAGAGGCA-3′ (SEQ ID NO: 691)5′-AAGAGGCAGGCUCCUGGCAAAAGGUCA-3′ (SEQ ID NO: 2000)3′-UUCUCCGUCCGAGGACCGUUUUCCAGU-5′ (SEQ ID NO: 365) MYC-1401 Target:5′-AAGAGGCAGGCTCCTGGCAAAAGGTCA-3′ (SEQ ID NO: 692)5′-GCAGGCUCCUGGCAAAAGGUCAGAGUC-3′ (SEQ ID NO: 2001)3′-CGUCCGAGGACCGUUUUCCAGUCUCAG-5′ (SEQ ID NO: 366) MYC-1406 Target:5′-GCAGGCTCCTGGCAAAAGGTCAGAGTC-3′ (SEQ ID NO: 693)5′-CUCCUGGCAAAAGGUCAGAGUCUGGAU-3′ (SEQ ID NO: 2002)3′-GAGGACCGUUUUCCAGUCUCAGACCUA-5′ (SEQ ID NO: 367) MYC-1411 Target:5′-CTCCTGGCAAAAGGTCAGAGTCTGGAT-3′ (SEQ ID NO: 694)5′-GGCAAAAGGUCAGAGUCUGGAUCACCU-3′ (SEQ ID NO: 2003)3′-CCGUUUUCCAGUCUCAGACCUAGUGGA-5′ (SEQ ID NO: 368) MYC-1416 Target:5′-GGCAAAAGGTCAGAGTCTGGATCACCT-3′ (SEQ ID NO: 695)5′-AAGGUCAGAGUCUGGAUCACCUUCUGC-3′ (SEQ ID NO: 2004)3′-UUCCAGUCUCAGACCUAGUGGAAGACG-5′ (SEQ ID NO: 369) MYC-1421 Target:5′-AAGGTCAGAGTCTGGATCACCTTCTGC-3′ (SEQ ID NO: 696)5′-CAGCAAACCUCCUCACAGCCCACUGGU-3′ (SEQ ID NO: 2005)3′-GUCGUUUGGAGGAGUGUCGGGUGACCA-5′ (SEQ ID NO: 370) MYC-1457 Target:5′-CAGCAAACCTCCTCACAGCCCACTGGT-3′ (SEQ ID NO: 697)5′-CUCCUCACAGCCCACUGGUCCUCAAGA-3′ (SEQ ID NO: 2006)3′-GAGGAGUGUCGGGUGACCAGGAGUUCU-5′ (SEQ ID NO: 371) MYC-1465 Target:5′-CTCCTCACAGCCCACTGGTCCTCAAGA-3′ (SEQ ID NO: 698)5′-CUCCCUCCACUCGGAAGGACUAUCCUG-3′ (SEQ ID NO: 2007)3′-GAGGGAGGUGAGCCUUCCUGAUAGGAC-5′ (SEQ ID NO: 372) MYC-1531 Target:5′-CTCCCTCCACTCGGAAGGACTATCCTG-3′ (SEQ ID NO: 699)5′-CACUCGGAAGGACUAUCCUGCUGCCAA-3′ (SEQ ID NO: 2008)3′-GUGAGCCUUCCUGAUAGGACGACGGUU-5′ (SEQ ID NO: 373) MYC-1538 Target:5′-CACTCGGAAGGACTATCCTGCTGCCAA-3′ (SEQ ID NO: 700)5′-CUAUCCUGCUGCCAAGAGGGUCAAGUU-3′ (SEQ ID NO: 2009)3′-GAUAGGACGACGGUUCUCCCAGUUCAA-5′ (SEQ ID NO: 374) MYC-1550 Target:5′-CTATCCTGCTGCCAAGAGGGTCAAGTT-3′ (SEQ ID NO: 701)5′-CUGCUGCCAAGAGGGUCAAGUUGGACA-3′ (SEQ ID NO: 2010)3′-GACGACGGUUCUCCCAGUUCAACCUGU-5′ (SEQ ID NO: 375) MYC-1555 Target:5′-CTGCTGCCAAGAGGGTCAAGTTGGACA-3′ (SEQ ID NO: 702)5′-GCCAAGAGGGUCAAGUUGGACAGUGUC-3′ (SEQ ID NO: 2011)3′-CGGUUCUCCCAGUUCAACCUGUCACAG-5′ (SEQ ID NO: 376) MYC-1560 Target:5′-GCCAAGAGGGTCAAGTTGGACAGTGTC-3′ (SEQ ID NO: 703)5′-GAGGGUCAAGUUGGACAGUGUCAGAGU-3′ (SEQ ID NO: 2012)3′-CUCCCAGUUCAACCUGUCACAGUCUCA-5′ (SEQ ID NO: 377) MYC-1565 Target:5′-GAGGGTCAAGTTGGACAGTGTCAGAGT-3′ (SEQ ID NO: 704)5′-UCAAGUUGGACAGUGUCAGAGUCCUGA-3′ (SEQ ID NO: 2013)3′-AGUUCAACCUGUCACAGUCUCAGGACU-5′ (SEQ ID NO: 378) MYC-1570 Target:5′-TCAAGTTGGACAGTGTCAGAGTCCTGA-3′ (SEQ ID NO: 705)5′-UUGGACAGUGUCAGAGUCCUGAGACAG-3′ (SEQ ID NO: 2014)3′-AACCUGUCACAGUCUCAGGACUCUGUC-5′ (SEQ ID NO: 379) MYC-1575 Target:5′-TTGGACAGTGTCAGAGTCCTGAGACAG-3′ (SEQ ID NO: 706)5′-GUCAGAGUCCUGAGACAGAUCAGCAAC-3′ (SEQ ID NO: 2015)3′-CAGUCUCAGGACUCUGUCUAGUCGUUG-5′ (SEQ ID NO: 380) MYC-1584 Target:5′-GTCAGAGTCCTGAGACAGATCAGCAAC-3′ (SEQ ID NO: 707)5′-CUGAGACAGAUCAGCAACAACCGAAAA-3′ (SEQ ID NO: 2016)3′-GACUCUGUCUAGUCGUUGUUGGCUUUU-5′ (SEQ ID NO: 381) MYC-1593 Target:5′-CTGAGACAGATCAGCAACAACCGAAAA-3′ (SEQ ID NO: 708)5′-CAGAUCAGCAACAACCGAAAAUGCACC-3′ (SEQ ID NO: 2017)3′-GUCUAGUCGUUGUUGGCUUUUACGUGG-5′ (SEQ ID NO: 382) MYC-1599 Target:5′-CAGATCAGCAACAACCGAAAATGCACC-3′ (SEQ ID NO: 709)5′-GUCCUCGGACACCGAGGAGAAUGUCAA-3′ (SEQ ID NO: 2018)3′-CAGGAGCCUGUGGCUCCUCUUACAGUU-5′ (SEQ ID NO: 383) MYC-1634 Target:5′-GTCCTCGGACACCGAGGAGAATGTCAA-3′ (SEQ ID NO: 710)5′-CGGACACCGAGGAGAAUGUCAAGAGGC-3′ (SEQ ID NO: 2019)3′-GCCUGUGGCUCCUCUUACAGUUCUCCG-5′ (SEQ ID NO: 384) MYC-1639 Target:5′-CGGACACCGAGGAGAATGTCAAGAGGC-3′ (SEQ ID NO: 711)5′-GCCAGAGGAGGAACGAGCUAAAACGGA-3′ (SEQ ID NO: 2020)3′-CGGUCUCCUCCUUGCUCGAUUUUGCCU-5′ (SEQ ID NO: 385) MYC-1687 Target:5′-GCCAGAGGAGGAACGAGCTAAAACGGA-3′ (SEQ ID NO: 712)5′-GGAGGAACGAGCUAAAACGGAGCUUUU-3′ (SEQ ID NO: 2021)3′-CCUCCUUGCUCGAUUUUGCCUCGAAAA-5′ (SEQ ID NO: 386) MYC-1693 Target:5′-GGAGGAACGAGCTAAAACGGAGCTTTT-3′ (SEQ ID NO: 713)5′-AACGAGCUAAAACGGAGCUUUUUUGCC-3′ (SEQ ID NO: 2022)3′-UUGCUCGAUUUUGCCUCGAAAAAACGG-5′ (SEQ ID NO: 387) MYC-1698 Target:5′-AACGAGCTAAAACGGAGCTTTTTTGCC-3′ (SEQ ID NO: 714)5′-CUAAAACGGAGCUUUUUUGCCCUGCGU-3′ (SEQ ID NO: 2023)3′-GAUUUUGCCUCGAAAAAACGGGACGCA-5′ (SEQ ID NO: 388) MYC-1704 Target:5′-CTAAAACGGAGCTTTTTTGCCCTGCGT-3′ (SEQ ID NO: 715)5′-ACGGAGCUUUUUUGCCCUGCGUGACCA-3′ (SEQ ID NO: 2024)3′-UGCCUCGAAAAAACGGGACGCACUGGU-5′ (SEQ ID NO: 389) MYC-1709 Target:5′-ACGGAGCTTTTTTGCCCTGCGTGACCA-3′ (SEQ ID NO: 716)5′-GUGACCAGAUCCCGGAGUUGGAAAACA-3′ (SEQ ID NO: 2025)3′-CACUGGUCUAGGGCCUCAACCUUUUGU-5′ (SEQ ID NO: 390) MYC-1729 Target:5′-GTGACCAGATCCCGGAGTTGGAAAACA-3′ (SEQ ID NO: 717)5′-CAGAUCCCGGAGUUGGAAAACAAUGAA-3′ (SEQ ID NO: 2026)3′-GUCUAGGGCCUCAACCUUUUGUUACUU-5′ (SEQ ID NO: 391) MYC-1734 Target:5′-CAGATCCCGGAGTTGGAAAACAATGAA-3′ (SEQ ID NO: 718)5′-CCCGGAGUUGGAAAACAAUGAAAAGGC-3′ (SEQ ID NO: 2027)3′-GGGCCUCAACCUUUUGUUACUUUUCCG-5′ (SEQ ID NO: 392) MYC-1739 Target:5′-CCCGGAGTTGGAAAACAATGAAAAGGC-3′ (SEQ ID NO: 719)5′-CAAGGUAGUUAUCCUUAAAAAAGCCAC-3′ (SEQ ID NO: 2028)3′-GUUCCAUCAAUAGGAAUUUUUUCGGUG-5′ (SEQ ID NO: 393) MYC-1769 Target:5′-CAAGGTAGTTATCCTTAAAAAAGCCAC-3′ (SEQ ID NO: 720)5′-UAGUUAUCCUUAAAAAAGCCACAGCAU-3′ (SEQ ID NO: 2029)3′-AUCAAUAGGAAUUUUUUCGGUGUCGUA-5′ (SEQ ID NO: 394) MYC-1774 Target:5′-TAGTTATCCTTAAAAAAGCCACAGCAT-3′ (SEQ ID NO: 721)5′-AUCCUUAAAAAAGCCACAGCAUACAUC-3′ (SEQ ID NO: 2030)3′-UAGGAAUUUUUUCGGUGUCGUAUGUAG-5′ (SEQ ID NO: 395) MYC-1779 Target:5′-ATCCTTAAAAAAGCCACAGCATACATC-3′ (SEQ ID NO: 722)5′-UAAAAAAGCCACAGCAUACAUCCUGUC-3′ (SEQ ID NO: 2031)3′-AUUUUUUCGGUGUCGUAUGUAGGACAG-5′ (SEQ ID NO: 396) MYC-1784 Target:5′-TAAAAAAGCCACAGCATACATCCTGTC-3′ (SEQ ID NO: 723)5′-AAGCCACAGCAUACAUCCUGUCCGUCC-3′ (SEQ ID NO: 2032)3′-UUCGGUGUCGUAUGUAGGACAGGCAGG-5′ (SEQ ID NO: 397) MYC-1789 Target:5′-AAGCCACAGCATACATCCTGTCCGTCC-3′ (SEQ ID NO: 724)5′-CAGCAUACAUCCUGUCCGUCCAAGCAG-3′ (SEQ ID NO: 2033)3′-GUCGUAUGUAGGACAGGCAGGUUCGUC-5′ (SEQ ID NO: 398) MYC-1795 Target:5′-CAGCATACATCCTGTCCGTCCAAGCAG-3′ (SEQ ID NO: 725)5′-AUCCUGUCCGUCCAAGCAGAGGAGCAA-3′ (SEQ ID NO: 2034)3′-UAGGACAGGCAGGUUCGUCUCCUCGUU-5′ (SEQ ID NO: 399) MYC-1803 Target:5′-ATCCTGTCCGTCCAAGCAGAGGAGCAA-3′ (SEQ ID NO: 726)5′-GUCCGUCCAAGCAGAGGAGCAAAAGCU-3′ (SEQ ID NO: 2035)3′-CAGGCAGGUUCGUCUCCUCGUUUUCGA-5′ (SEQ ID NO: 400) MYC-1808 Target:5′-GTCCGTCCAAGCAGAGGAGCAAAAGCT-3′ (SEQ ID NO: 727)5′-AAGCAGAGGAGCAAAAGCUCAUUUCUG-3′ (SEQ ID NO: 2036)3′-UUCGUCUCCUCGUUUUCGAGUAAAGAC-5′ (SEQ ID NO: 401) MYC-1816 Target:5′-AAGCAGAGGAGCAAAAGCTCATTTCTG-3′ (SEQ ID NO: 728)5′-GGAGCAAAAGCUCAUUUCUGAAGAGGA-3′ (SEQ ID NO: 2037)3′-CCUCGUUUUCGAGUAAAGACUUCUCCU-5′ (SEQ ID NO: 402) MYC-1823 Target:5′-GGAGCAAAAGCTCATTTCTGAAGAGGA-3′ (SEQ ID NO: 729)5′-AAAAGCUCAUUUCUGAAGAGGACUUGU-3′ (SEQ ID NO: 2038)3′-UUUUCGAGUAAAGACUUCUCCUGAACA-5′ (SEQ ID NO: 403) MYC-1828 Target:5′-AAAAGCTCATTTCTGAAGAGGACTTGT-3′ (SEQ ID NO: 730)5′-UCAUUUCUGAAGAGGACUUGUUGCGGA-3′ (SEQ ID NO: 2039)3′-AGUAAAGACUUCUCCUGAACAACGCCU-5′ (SEQ ID NO: 404) MYC-1834 Target:5′-TCATTTCTGAAGAGGACTTGTTGCGGA-3′ (SEQ ID NO: 731)5′-CUGAAGAGGACUUGUUGCGGAAACGAC-3′ (SEQ ID NO: 2040)3′-GACUUCUCCUGAACAACGCCUUUGCUG-5′ (SEQ ID NO: 405) MYC-1840 Target:5′-CTGAAGAGGACTTGTTGCGGAAACGAC-3′ (SEQ ID NO: 732)5′-GAGGACUUGUUGCGGAAACGACGAGAA-3′ (SEQ ID NO: 2041)3′-CUCCUGAACAACGCCUUUGCUGCUCUU-5′ (SEQ ID NO: 406) MYC-1845 Target:5′-GAGGACTTGTTGCGGAAACGACGAGAA-3′ (SEQ ID NO: 733)5′-CUUGUUGCGGAAACGACGAGAACAGUU-3′ (SEQ ID NO: 2042)3′-GAACAACGCCUUUGCUGCUCUUGUCAA-5′ (SEQ ID NO: 407) MYC-1850 Target:5′-CTTGTTGCGGAAACGACGAGAACAGTT-3′ (SEQ ID NO: 734)5′-UGCGGAAACGACGAGAACAGUUGAAAC-3′ (SEQ ID NO: 2043)3′-ACGCCUUUGCUGCUCUUGUCAACUUUG-5′ (SEQ ID NO: 408) MYC-1855 Target:5′-TGCGGAAACGACGAGAACAGTTGAAAC-3′ (SEQ ID NO: 735)5′-ACAAACUUGAACAGCUACGGAACUCUU-3′ (SEQ ID NO: 2044)3′-UGUUUGAACUUGUCGAUGCCUUGAGAA-5′ (SEQ ID NO: 409) MYC-1882 Target:5′-ACAAACTTGAACAGCTACGGAACTCTT-3′ (SEQ ID NO: 736)5′-UUGAACAGCUACGGAACUCUUGUGCGU-3′ (SEQ ID NO: 2045)3′-AACUUGUCGAUGCCUUGAGAACACGCA-5′ (SEQ ID NO: 410) MYC-1888 Target:5′-TTGAACAGCTACGGAACTCTTGTGCGT-3′ (SEQ ID NO: 737)5′-CAGCUACGGAACUCUUGUGCGUAAGGA-3′ (SEQ ID NO: 2046)3′-GUCGAUGCCUUGAGAACACGCAUUCCU-5′ (SEQ ID NO: 411) MYC-1893 Target:5′-CAGCTACGGAACTCTTGTGCGTAAGGA-3′ (SEQ ID NO: 738)5′-GGAACUCUUGUGCGUAAGGAAAAGUAA-3′ (SEQ ID NO: 2047)3′-CCUUGAGAACACGCAUUCCUUUUCAUU-5′ (SEQ ID NO: 412) MYC-1900 Target:5′-GGAACTCTTGTGCGTAAGGAAAAGTAA-3′ (SEQ ID NO: 739)5′-CUUGUGCGUAAGGAAAAGUAAGGAAAA-3′ (SEQ ID NO: 2048)3′-GAACACGCAUUCCUUUUCAUUCCUUUU-5′ (SEQ ID NO: 413) MYC-1906 Target:5′-CTTGTGCGTAAGGAAAAGTAAGGAAAA-3′ (SEQ ID NO: 740)5′-GCGUAAGGAAAAGUAAGGAAAACGAUU-3′ (SEQ ID NO: 2049)3′-CGCAUUCCUUUUCAUUCCUUUUGCUAA-5′ (SEQ ID NO: 414) MYC-1911 Target:5′-GCGTAAGGAAAAGTAAGGAAAACGATT-3′ (SEQ ID NO: 741)5′-AAGUAAGGAAAACGAUUCCUUCUAACA-3′ (SEQ ID NO: 2050)3′-UUCAUUCCUUUUGCUAAGGAAGAUUGU-5′ (SEQ ID NO: 415) MYC-1921 Target:5′-AAGTAAGGAAAACGATTCCTTCTAACA-3′ (SEQ ID NO: 742)5′-AGGAAAACGAUUCCUUCUAACAGAAAU-3′ (SEQ ID NO: 2051)3′-UCCUUUUGCUAAGGAAGAUUGUCUUUA-5′ (SEQ ID NO: 416) MYC-1926 Target:5′-AGGAAAACGATTCCTTCTAACAGAAAT-3′ (SEQ ID NO: 743)5′-AACGAUUCCUUCUAACAGAAAUGUCCU-3′ (SEQ ID NO: 2052)3′-UUGCUAAGGAAGAUUGUCUUUACAGGA-5′ (SEQ ID NO: 417) MYC-1931 Target:5′-AACGATTCCTTCTAACAGAAATGTCCT-3′ (SEQ ID NO: 744)5′-UCCUUCUAACAGAAAUGUCCUGAGCAA-3′ (SEQ ID NO: 2053)3′-AGGAAGAUUGUCUUUACAGGACUCGUU-5′ (SEQ ID NO: 418) MYC-1937 Target:5′-TCCTTCTAACAGAAATGTCCTGAGCAA-3′ (SEQ ID NO: 745)5′-AACAGAAAUGUCCUGAGCAAUCACCUA-3′ (SEQ ID NO: 2054)3′-UUGUCUUUACAGGACUCGUUAGUGGAU-5′ (SEQ ID NO: 419) MYC-1944 Target:5′-AACAGAAATGTCCTGAGCAATCACCTA-3′ (SEQ ID NO: 746)5′-GUCCUGAGCAAUCACCUAUGAACUUGU-3′ (SEQ ID NO: 2055)3′-CAGGACUCGUUAGUGGAUACUUGAACA-5′ (SEQ ID NO: 420) MYC-1953 Target:5′-GTCCTGAGCAATCACCTATGAACTTGT-3′ (SEQ ID NO: 747)5′-AGCAAUCACCUAUGAACUUGUUUCAAA-3′ (SEQ ID NO: 2056)3′-UCGUUAGUGGAUACUUGAACAAAGUUU-5′ (SEQ ID NO: 421) MYC-1959 Target:5′-AGCAATCACCTATGAACTTGTTTCAAA-3′ (SEQ ID NO: 748)5′-CACCUAUGAACUUGUUUCAAAUGCAUG-3′ (SEQ ID NO: 2057)3′-GUGGAUACUUGAACAAAGUUUACGUAC-5′ (SEQ ID NO: 422) MYC-1965 Target:5′-CACCTATGAACTTGTTTCAAATGCATG-3′ (SEQ ID NO: 749)5′-AUGAACUUGUUUCAAAUGCAUGAUCAA-3′ (SEQ ID NO: 2058)3′-UACUUGAACAAAGUUUACGUACUAGUU-5′ (SEQ ID NO: 423) MYC-1970 Target:5′-ATGAACTTGTTTCAAATGCATGATCAA-3′ (SEQ ID NO: 750)5′-UUGUUUCAAAUGCAUGAUCAAAUGCAA-3′ (SEQ ID NO: 2059)3′-AACAAAGUUUACGUACUAGUUUACGUU-5′ (SEQ ID NO: 424) MYC-1976 Target:5′-TTGTTTCAAATGCATGATCAAATGCAA-3′ (SEQ ID NO: 751)5′-UCAAAUGCAUGAUCAAAUGCAACCUCA-3′ (SEQ ID NO: 2060)3′-AGUUUACGUACUAGUUUACGUUGGAGU-5′ (SEQ ID NO: 425) MYC-1981 Target:5′-TCAAATGCATGATCAAATGCAACCTCA-3′ (SEQ ID NO: 752)5′-AUGAUCAAAUGCAACCUCACAACCUUG-3′ (SEQ ID NO: 2061)3′-UACUAGUUUACGUUGGAGUGUUGGAAC-5′ (SEQ ID NO: 426) MYC-1989 Target:5′-ATGATCAAATGCAACCTCACAACCTTG-3′ (SEQ ID NO: 753)5′-CAAAUGCAACCUCACAACCUUGGCUGA-3′ (SEQ ID NO: 2062)3′-GUUUACGUUGGAGUGUUGGAACCGACU-5′ (SEQ ID NO: 427) MYC-1994 Target:5′-CAAATGCAACCTCACAACCTTGGCTGA-3′ (SEQ ID NO: 754)5′-AACCUCACAACCUUGGCUGAGUCUUGA-3′ (SEQ ID NO: 2063)3′-UUGGAGUGUUGGAACCGACUCAGAACU-5′ (SEQ ID NO: 428) MYC-2001 Target:5′-AACCTCACAACCTTGGCTGAGTCTTGA-3′ (SEQ ID NO: 755)5′-CACAACCUUGGCUGAGUCUUGAGACUG-3′ (SEQ ID NO: 2064)3′-GUGUUGGAACCGACUCAGAACUCUGAC-5′ (SEQ ID NO: 429) MYC-2006 Target:5′-CACAACCTTGGCTGAGTCTTGAGACTG-3′ (SEQ ID NO: 756)5′-UUGGCUGAGUCUUGAGACUGAAAGAUU-3′ (SEQ ID NO: 2065)3′-AACCGACUCAGAACUCUGACUUUCUAA-5′ (SEQ ID NO: 430) MYC-2013 Target:5′-TTGGCTGAGTCTTGAGACTGAAAGATT-3′ (SEQ ID NO: 757)5′-GAGUCUUGAGACUGAAAGAUUUAGCCA-3′ (SEQ ID NO: 2066)3′-CUCAGAACUCUGACUUUCUAAAUCGGU-5′ (SEQ ID NO: 431) MYC-2019 Target:5′-GAGTCTTGAGACTGAAAGATTTAGCCA-3′ (SEQ ID NO: 758)5′-GAGACUGAAAGAUUUAGCCAUAAUGUA-3′ (SEQ ID NO: 2067)3′-CUCUGACUUUCUAAAUCGGUAUUACAU-5′ (SEQ ID NO: 432) MYC-2026 Target:5′-GAGACTGAAAGATTTAGCCATAATGTA-3′ (SEQ ID NO: 759)5′-UGAAAGAUUUAGCCAUAAUGUAAACUG-3′ (SEQ ID NO: 2068)3′-ACUUUCUAAAUCGGUAUUACAUUUGAC-5′ (SEQ ID NO: 433) MYC-2031 Target:5′-TGAAAGATTTAGCCATAATGTAAACTG-3′ (SEQ ID NO: 760)5′-UAGCCAUAAUGUAAACUGCCUCAAAUU-3′ (SEQ ID NO: 2069)3′-AUCGGUAUUACAUUUGACGGAGUUUAA-5′ (SEQ ID NO: 434) MYC-2040 Target:5′-TAGCCATAATGTAAACTGCCTCAAATT-3′ (SEQ ID NO: 761)5′-AUGUAAACUGCCUCAAAUUGGACUUUG-3′ (SEQ ID NO: 2070)3′-UACAUUUGACGGAGUUUAACCUGAAAC-5′ (SEQ ID NO: 435) MYC-2048 Target:5′-ATGTAAACTGCCTCAAATTGGACTTTG-3′ (SEQ ID NO: 762)5′-ACUGCCUCAAAUUGGACUUUGGGCAUA-3′ (SEQ ID NO: 2071)3′-UGACGGAGUUUAACCUGAAACCCGUAU-5′ (SEQ ID NO: 436) MYC-2054 Target:5′-ACTGCCTCAAATTGGACTTTGGGCATA-3′ (SEQ ID NO: 763)5′-CUCAAAUUGGACUUUGGGCAUAAAAGA-3′ (SEQ ID NO: 2072)3′-GAGUUUAACCUGAAACCCGUAUUUUCU-5′ (SEQ ID NO: 437) MYC-2059 Target:5′-CTCAAATTGGACTTTGGGCATAAAAGA-3′ (SEQ ID NO: 764)5′-UGGACUUUGGGCAUAAAAGAACUUUUU-3′ (SEQ ID NO: 2073)3′-ACCUGAAACCCGUAUUUUCUUGAAAAA-5′ (SEQ ID NO: 438) MYC-2066 Target:5′-TGGACTTTGGGCATAAAAGAACTTTTT-3′ (SEQ ID NO: 765)5′-UGGGCAUAAAAGAACUUUUUUAUGCUU-3′ (SEQ ID NO: 2074)3′-ACCCGUAUUUUCUUGAAAAAAUACGAA-5′ (SEQ ID NO: 439) MYC-2073 Target:5′-TGGGCATAAAAGAACTTTTTTATGCTT-3′ (SEQ ID NO: 766)5′-AUAAAAGAACUUUUUUAUGCUUACCAU-3′ (SEQ ID NO: 2075)3′-UAUUUUCUUGAAAAAAUACGAAUGGUA-5′ (SEQ ID NO: 440) MYC-2078 Target:5′-ATAAAAGAACTTTTTTATGCTTACCAT-3′ (SEQ ID NO: 767)5′-AGAACUUUUUUAUGCUUACCAUCUUUU-3′ (SEQ ID NO: 2076)3′-UCUUGAAAAAAUACGAAUGGUAGAAAA-5′ (SEQ ID NO: 441) MYC-2083 Target:5′-AGAACTTTTTTATGCTTACCATCTTTT-3′ (SEQ ID NO: 768)5′-UUUUUAUGCUUACCAUCUUUUUUUUUU-3′ (SEQ ID NO: 2077)3′-AAAAAUACGAAUGGUAGAAAAAAAAAA-5′ (SEQ ID NO: 442) MYC-2089 Target:5′-TTTTTATGCTTACCATCTTTTTTTTTT-3′ (SEQ ID NO: 769)5′-AUGCUUACCAUCUUUUUUUUUUCUUUA-3′ (SEQ ID NO: 2078)3′-UACGAAUGGUAGAAAAAAAAAAGAAAU-5′ (SEQ ID NO: 443) MYC-2094 Target:5′-ATGCTTACCATCTTTTTTTTTTCTTTA-3′ (SEQ ID NO: 770)5′-UACCAUCUUUUUUUUUUCUUUAACAGA-3′ (SEQ ID NO: 2079)3′-AUGGUAGAAAAAAAAAAGAAAUUGUCU-5′ (SEQ ID NO: 444) MYC-2099 Target:5′-TACCATCTTTTTTTTTTCTTTAACAGA-3′ (SEQ ID NO: 771)5′-CUUUUUUUUUUCUUUAACAGAUUUGUA-3′ (SEQ ID NO: 2080)3′-GAAAAAAAAAAGAAAUUGUCUAAACAU-5′ (SEQ ID NO: 445) MYC-2105 Target:5′-CTTTTTTTTTTCTTTAACAGATTTGTA-3′ (SEQ ID NO: 772)5′-UUCUUUAACAGAUUUGUAUUUAAGAAU-3′ (SEQ ID NO: 2081)3′-AAGAAAUUGUCUAAACAUAAAUUCUUA-5′ (SEQ ID NO: 446) MYC-2114 Target:5′-TTCTTTAACAGATTTGTATTTAAGAAT-3′ (SEQ ID NO: 773)5′-AACAGAUUUGUAUUUAAGAAUUGUUUU-3′ (SEQ ID NO: 2082)3′-UUGUCUAAACAUAAAUUCUUAACAAAA-5′ (SEQ ID NO: 447) MYC-2120 Target:5′-AACAGATTTGTATTTAAGAATTGTTTT-3′ (SEQ ID NO: 774)5′-UGUAUUUAAGAAUUGUUUUUAAAAAAU-3′ (SEQ ID NO: 2083)3′-ACAUAAAUUCUUAACAAAAAUUUUUUA-5′ (SEQ ID NO: 448) MYC-2128 Target:5′-TGTATTTAAGAATTGTTTTTAAAAAAT-3′ (SEQ ID NO: 775)5′-AAGAAUUGUUUUUAAAAAAUUUUAAGA-3′ (SEQ ID NO: 2084)3′-UUCUUAACAAAAAUUUUUUAAAAUUCU-5′ (SEQ ID NO: 449) MYC-2135 Target:5′-AAGAATTGTTTTTAAAAAATTTTAAGA-3′ (SEQ ID NO: 776)5′-ACAAUGUUUCUCUGUAAAUAUUGCCAU-3′ (SEQ ID NO: 2085)3′-UGUUACAAAGAGACAUUUAUAACGGUA-5′ (SEQ ID NO: 450) MYC-2167 Target:5′-ACAATGTTTCTCTGTAAATATTGCCAT-3′ (SEQ ID NO: 777)5′-CUCUGUAAAUAUUGCCAUUAAAUGUAA-3′ (SEQ ID NO: 2086)3′-GAGACAUUUAUAACGGUAAUUUACAUU-5′ (SEQ ID NO: 451) MYC-2176 Target:5′-CTCTGTAAATATTGCCATTAAATGTAA-3′ (SEQ ID NO: 778)5′-UAAAUAUUGCCAUUAAAUGUAAAUAAC-3′ (SEQ ID NO: 2087)3′-AUUUAUAACGGUAAUUUACAUUUAUUG-5′ (SEQ ID NO: 452) MYC-2181 Target:5′-TAAATATTGCCATTAAATGTAAATAAC-3′ (SEQ ID NO: 779)5′-UGCCAUUAAAUGUAAAUAACUUUAAUA-3′ (SEQ ID NO: 2088)3′-ACGGUAAUUUACAUUUAUUGAAAUUAU-5′ (SEQ ID NO: 453) MYC-2188 Target:5′-TGCCATTAAATGTAAATAACTTTAATA-3′ (SEQ ID NO: 780)5′-CUUUAAUAAAACGUUUAUAGCAGUUAC-3′ (SEQ ID NO: 2089)3′-GAAAUUAUUUUGCAAAUAUCGUCAAUG-5′ (SEQ ID NO: 454) MYC-2207 Target:5′-CTTTAATAAAACGTTTATAGCAGTTAC-3′ (SEQ ID NO: 781)5′-CACAGAAUUUCAAUCCUAGUAUAUAGU-3′ (SEQ ID NO: 2090)3′-GUGUCUUAAAGUUAGGAUCAUAUAUCA-5′ (SEQ ID NO: 455) MYC-2233 Target:5′-CACAGAATTTCAATCCTAGTATATAGT-3′ (SEQ ID NO: 782)5′-ACCUAGUAUUAUAGGUACUAUAAACCC-3′ (SEQ ID NO: 2091)3′-UGGAUCAUAAUAUCCAUGAUAUUUGGG-5′ (SEQ ID NO: 456) MYC-2260 Target:5′-ACCTAGTATTATAGGTACTATAAACCC-3′ (SEQ ID NO: 783)5′-AUUAUAGGUACUAUAAACCCUAAUUUU-3′ (SEQ ID NO: 2092)3′-UAAUAUCCAUGAUAUUUGGGAUUAAAA-5′ (SEQ ID NO: 457) MYC-2267 Target:5′-ATTATAGGTACTATAAACCCTAATTTT-3′ (SEQ ID NO: 784)5′-GUACUAUAAACCCUAAUUUUUUUUAUU-3′ (SEQ ID NO: 2093)3′-CAUGAUAUUUGGGAUUAAAAAAAAUAA-5′ (SEQ ID NO: 458) MYC-2274 Target:5′-GTACTATAAACCCTAATTTTTTTTATT-3′ (SEQ ID NO: 785)5′-AACCCUAAUUUUUUUUAUUUAAGUACA-3′ (SEQ ID NO: 2094)3′-UUGGGAUUAAAAAAAAUAAAUUCAUGU-5′ (SEQ ID NO: 459) MYC-2282 Target:5′-AACCCTAATTTTTTTTATTTAAGTACA-3′ (SEQ ID NO: 786)5′-UAAUUUUUUUUAUUUAAGUACAUUUUG-3′ (SEQ ID NO: 2095)3′-AUUAAAAAAAAUAAAUUCAUGUAAAAC-5′ (SEQ ID NO: 460) MYC-2287 Target:5′-TAATTTTTTTTATTTAAGTACATTTTG-3′ (SEQ ID NO: 787)5′-UUUAUUUAAGUACAUUUUGCUUUUUAA-3′ (SEQ ID NO: 2096)3′-AAAUAAAUUCAUGUAAAACGAAAAAUU-5′ (SEQ ID NO: 461) MYC-2295 Target:5′-TTTATTTAAGTACATTTTGCTTTTTAA-3′ (SEQ ID NO: 788)5′-UUAAGUACAUUUUGCUUUUUAAAGUUG-3′ (SEQ ID NO: 2097)3′-AAUUCAUGUAAAACGAAAAAUUUCAAC-5′ (SEQ ID NO: 462) MYC-2300 Target:5′-TTAAGTACATTTTGCTTTTTAAAGTTG-3′ (SEQ ID NO: 789)5′-ACAUUUUGCUUUUUAAAGUUGAUUUUU-3′ (SEQ ID NO: 2098)3′-UGUAAAACGAAAAAUUUCAACUAAAAA-5′ (SEQ ID NO: 463) MYC-2306 Target:5′-ACATTTTGCTTTTTAAAGTTGATTTTT-3′ (SEQ ID NO: 790)5′-UGCUUUUUAAAGUUGAUUUUUUUCUAU-3′ (SEQ ID NO: 2099)3′-ACGAAAAAUUUCAACUAAAAAAAGAUA-5′ (SEQ ID NO: 464) MYC-2312 Target:5′-TGCTTTTTAAAGTTGATTTTTTTCTAT-3′ (SEQ ID NO: 791)5′-UCUAUUGUUUUUAGAAAAAAUAAAAUA-3′ (SEQ ID NO: 2100)3′-AGAUAACAAAAAUCUUUUUUAUUUUAU-5′ (SEQ ID NO: 465) MYC-2334 Target:5′-TCTATTGTTTTTAGAAAAAATAAAATA-3′ (SEQ ID NO: 792)5′-UGUUUUUAGAAAAAAUAAAAUAACUGG-3′ (SEQ ID NO: 2101)3′-ACAAAAAUCUUUUUUAUUUUAUUGACC-5′ (SEQ ID NO: 466) MYC-2339 Target:5′-TGTTTTTAGAAAAAATAAAATAACTGG-3′ (SEQ ID NO: 793)5′-GAAAAAAUAAAAUAACUGGCAAAUAUA-3′ (SEQ ID NO: 2102)3′-CUUUUUUAUUUUAUUGACCGUUUAUAU-5′ (SEQ ID NO: 467) MYC-2347 Target:5′-GAAAAAATAAAATAACTGGCAAATATA-3′ (SEQ ID NO: 794)5′-AAAAUAACUGGCAAAUAUAUCAUUGAG-3′ (SEQ ID NO: 2103)3′-UUUUAUUGACCGUUUAUAUAGUAACUC-5′ (SEQ ID NO: 468) MYC-2355 Target:5′-AAAATAACTGGCAAATATATCATTGAG-3′ (SEQ ID NO: 795)5′-GGCAAAUAUAUCAUUGAGCCAAAUCUU-3′ (SEQ ID NO: 2104)3′-CCGUUUAUAUAGUAACUCGGUUUAGAA-5′ (SEQ ID NO: 469) MYC-2364 Target:5′-GGCAAATATATCATTGAGCCAAATCTT-3′ (SEQ ID NO: 796)5′-AUAUCAUUGAGCCAAAUCUUAAAAAAA-3′ (SEQ ID NO: 2105)3′-UAUAGUAACUCGGUUUAGAAUUUUUUU-5′ (SEQ ID NO: 470) MYC-2371 Target:5′-ATATCATTGAGCCAAATCTTAAAAAAA-3′ (SEQ ID NO: 797)5′-UUGAGCCAAAUCUUAAAAAAAAAAAAA-3′ (SEQ ID NO: 2106)3′-AACUCGGUUUAGAAUUUUUUUUUUUUU-5′ (SEQ ID NO: 471) MYC-2377 Target:5′-TTGAGCCAAATCTTAAAAAAAAAAAAA-3′ (SEQ ID NO: 798)5′-UAACUCGCUGUAGUAAUUCCAGCGAGA-3′ (SEQ ID NO: 2107)3′-AUUGAGCGACAUCAUUAAGGUCGCUCU-5′ (SEQ ID NO: 472) MYC-188 Target:5′-TAACTCGCTGTAGTAATTCCAGCGAGA-3′ (SEQ ID NO: 799)5′-AACUCGCUGUAGUAAUUCCAGCGAGAG-3′ (SEQ ID NO: 2108)3′-UUGAGCGACAUCAUUAAGGUCGCUCUC-5′ (SEQ ID NO: 473) MYC-189 Target:5′-AACTCGCTGTAGTAATTCCAGCGAGAG-3′ (SEQ ID NO: 800)5′-ACUCGCUGUAGUAAUUCCAGCGAGAGG-3′ (SEQ ID NO: 2109)3′-UGAGCGACAUCAUUAAGGUCGCUCUCC-5′ (SEQ ID NO: 474) MYC-190 Target:5′-ACTCGCTGTAGTAATTCCAGCGAGAGG-3′ (SEQ ID NO: 801)5′-CUCGCUGUAGUAAUUCCAGCGAGAGGC-3′ (SEQ ID NO: 2110)3′-GAGCGACAUCAUUAAGGUCGCUCUCCG-5′ (SEQ ID NO: 475) MYC-191 Target:5′-CTCGCTGTAGTAATTCCAGCGAGAGGC-3′ (SEQ ID NO: 802)5′-UCGCUGUAGUAAUUCCAGCGAGAGGCA-3′ (SEQ ID NO: 2111)3′-AGCGACAUCAUUAAGGUCGCUCUCCGU-5′ (SEQ ID NO: 476) MYC-192 Target:5′-TCGCTGTAGTAATTCCAGCGAGAGGCA-3′ (SEQ ID NO: 803)5′-CGCUGUAGUAAUUCCAGCGAGAGGCAG-3′ (SEQ ID NO: 2112)3′-GCGACAUCAUUAAGGUCGCUCUCCGUC-5′ (SEQ ID NO: 477) MYC-193 Target:5′-CGCTGTAGTAATTCCAGCGAGAGGCAG-3′ (SEQ ID NO: 804)5′-GCUGUAGUAAUUCCAGCGAGAGGCAGA-3′ (SEQ ID NO: 2113)3′-CGACAUCAUUAAGGUCGCUCUCCGUCU-5′ (SEQ ID NO: 478) MYC-194 Target:5′-GCTGTAGTAATTCCAGCGAGAGGCAGA-3′ (SEQ ID NO: 805)5′-CUGUAGUAAUUCCAGCGAGAGGCAGAG-3′ (SEQ ID NO: 2114)3′-GACAUCAUUAAGGUCGCUCUCCGUCUC-5′ (SEQ ID NO: 479) MYC-195 Target:5′-CTGTAGTAATTCCAGCGAGAGGCAGAG-3′ (SEQ ID NO: 806)5′-AGCUUCACCAACAGGAACUAUGACCUC-3′ (SEQ ID NO: 2115)3′-UCGAAGUGGUUGUCCUUGAUACUGGAG-5′ (SEQ ID NO: 480) MYC-612 Target:5′-AGCTTCACCAACAGGAACTATGACCTC-3′ (SEQ ID NO: 807)5′-GCUUCACCAACAGGAACUAUGACCUCG-3′ (SEQ ID NO: 2116)3′-CGAAGUGGUUGUCCUUGAUACUGGAGC-5′ (SEQ ID NO: 481) MYC-613 Target:5′-GCTTCACCAACAGGAACTATGACCTCG-3′ (SEQ ID NO: 808)5′-CUUCACCAACAGGAACUAUGACCUCGA-3′ (SEQ ID NO: 2117)3′-GAAGUGGUUGUCCUUGAUACUGGAGCU-5′ (SEQ ID NO: 482) MYC-614 Target:5′-CTTCACCAACAGGAACTATGACCTCGA-3′ (SEQ ID NO: 809)5′-UUCACCAACAGGAACUAUGACCUCGAC-3′ (SEQ ID NO: 2118)3′-AAGUGGUUGUCCUUGAUACUGGAGCUG-5′ (SEQ ID NO: 483) MYC-615 Target:5′-TTCACCAACAGGAACTATGACCTCGAC-3′ (SEQ ID NO: 810)5′-UCACCAACAGGAACUAUGACCUCGACU-3′ (SEQ ID NO: 2119)3′-AGUGGUUGUCCUUGAUACUGGAGCUGA-5′ (SEQ ID NO: 484) MYC-616 Target:5′-TCACCAACAGGAACTATGACCTCGACT-3′ (SEQ ID NO: 811)5′-CACCAACAGGAACUAUGACCUCGACUA-3′ (SEQ ID NO: 2120)3′-GUGGUUGUCCUUGAUACUGGAGCUGAU-5′ (SEQ ID NO: 485) MYC-617 Target:5′-CACCAACAGGAACTATGACCTCGACTA-3′ (SEQ ID NO: 812)5′-ACCAACAGGAACUAUGACCUCGACUAC-3′ (SEQ ID NO: 2121)3′-UGGUUGUCCUUGAUACUGGAGCUGAUG-5′ (SEQ ID NO: 486) MYC-618 Target:5′-ACCAACAGGAACTATGACCTCGACTAC-3′ (SEQ ID NO: 813)5′-CCAACAGGAACUAUGACCUCGACUACG-3′ (SEQ ID NO: 2122)3′-GGUUGUCCUUGAUACUGGAGCUGAUGC-5′ (SEQ ID NO: 487) MYC-619 Target:5′-CCAACAGGAACTATGACCTCGACTACG-3′ (SEQ ID NO: 814)5′-CAACAGGAACUAUGACCUCGACUACGA-3′ (SEQ ID NO: 2123)3′-GUUGUCCUUGAUACUGGAGCUGAUGCU-5′ (SEQ ID NO: 488) MYC-620 Target:5′-CAACAGGAACTATGACCTCGACTACGA-3′ (SEQ ID NO: 815)5′-AACAGGAACUAUGACCUCGACUACGAC-3′ (SEQ ID NO: 2124)3′-UUGUCCUUGAUACUGGAGCUGAUGCUG-5′ (SEQ ID NO: 489) MYC-621 Target:5′-AACAGGAACTATGACCTCGACTACGAC-3′ (SEQ ID NO: 816)5′-ACAGGAACUAUGACCUCGACUACGACU-3′ (SEQ ID NO: 2125)3′-UGUCCUUGAUACUGGAGCUGAUGCUGA-5′ (SEQ ID NO: 490) MYC-622 Target:5′-ACAGGAACTATGACCTCGACTACGACT-3′ (SEQ ID NO: 817)5′-CAGGAACUAUGACCUCGACUACGACUC-3′ (SEQ ID NO: 2126)3′-GUCCUUGAUACUGGAGCUGAUGCUGAG-5′ (SEQ ID NO: 491) MYC-623 Target:5′-CAGGAACTATGACCTCGACTACGACTC-3′ (SEQ ID NO: 818)5′-AGGAACUAUGACCUCGACUACGACUCG-3′ (SEQ ID NO: 2127)3′-UCCUUGAUACUGGAGCUGAUGCUGAGC-5′ (SEQ ID NO: 492) MYC-624 Target:5′-AGGAACTATGACCTCGACTACGACTCG-3′ (SEQ ID NO: 819)5′-GGAACUAUGACCUCGACUACGACUCGG-3′ (SEQ ID NO: 2128)3′-CCUUGAUACUGGAGCUGAUGCUGAGCC-5′ (SEQ ID NO: 493) MYC-625 Target:5′-GGAACTATGACCTCGACTACGACTCGG-3′ (SEQ ID NO: 820)5′-GAACUAUGACCUCGACUACGACUCGGU-3′ (SEQ ID NO: 2129)3′-CUUGAUACUGGAGCUGAUGCUGAGCCA-5′ (SEQ ID NO: 494) MYC-626 Target:5′-GAACTATGACCTCGACTACGACTCGGT-3′ (SEQ ID NO: 821)5′-AACUAUGACCUCGACUACGACUCGGUG-3′ (SEQ ID NO: 2130)3′-UUGAUACUGGAGCUGAUGCUGAGCCAC-5′ (SEQ ID NO: 495) MYC-627 Target:5′-AACTATGACCTCGACTACGACTCGGTG-3′ (SEQ ID NO: 822)5′-ACUAUGACCUCGACUACGACUCGGUGC-3′ (SEQ ID NO: 2131)3′-UGAUACUGGAGCUGAUGCUGAGCCACG-5′ (SEQ ID NO: 496) MYC-628 Target:5′-ACTATGACCTCGACTACGACTCGGTGC-3′ (SEQ ID NO: 823)5′-CUAUGACCUCGACUACGACUCGGUGCA-3′ (SEQ ID NO: 2132)3′-GAUACUGGAGCUGAUGCUGAGCCACGU-5′ (SEQ ID NO: 497) MYC-629 Target:5′-CTATGACCTCGACTACGACTCGGTGCA-3′ (SEQ ID NO: 824)5′-GCGAGGAUAUCUGGAAGAAAUUCGAGC-3′ (SEQ ID NO: 2133)3′-CGCUCCUAUAGACCUUCUUUAAGCUCG-5′ (SEQ ID NO: 498) MYC-733 Target:5′-GCGAGGATATCTGGAAGAAATTCGAGC-3′ (SEQ ID NO: 825)5′-CGAGGAUAUCUGGAAGAAAUUCGAGCU-3′ (SEQ ID NO: 2134)3′-GCUCCUAUAGACCUUCUUUAAGCUCGA-5′ (SEQ ID NO: 499) MYC-734 Target:5′-CGAGGATATCTGGAAGAAATTCGAGCT-3′ (SEQ ID NO: 826)5′-GAGGAUAUCUGGAAGAAAUUCGAGCUG-3′ (SEQ ID NO: 2135)3′-CUCCUAUAGACCUUCUUUAAGCUCGAC-5′ (SEQ ID NO: 500) MYC-735 Target:5′-GAGGATATCTGGAAGAAATTCGAGCTG-3′ (SEQ ID NO: 827)5′-AGGAUAUCUGGAAGAAAUUCGAGCUGC-3′ (SEQ ID NO: 2136)3′-UCCUAUAGACCUUCUUUAAGCUCGACG-5′ (SEQ ID NO: 501) MYC-736 Target:5′-AGGATATCTGGAAGAAATTCGAGCTGC-3′ (SEQ ID NO: 828)5′-GGAUAUCUGGAAGAAAUUCGAGCUGCU-3′ (SEQ ID NO: 2137)3′-CCUAUAGACCUUCUUUAAGCUCGACGA-5′ (SEQ ID NO: 502) MYC-737 Target:5′-GGATATCTGGAAGAAATTCGAGCTGCT-3′ (SEQ ID NO: 829)5′-GAUAUCUGGAAGAAAUUCGAGCUGCUG-3′ (SEQ ID NO: 2138)3′-CUAUAGACCUUCUUUAAGCUCGACGAC-5′ (SEQ ID NO: 503) MYC-738 Target:5′-GATATCTGGAAGAAATTCGAGCTGCTG-3′ (SEQ ID NO: 830)5′-AUAUCUGGAAGAAAUUCGAGCUGCUGC-3′ (SEQ ID NO: 2139)3′-UAUAGACCUUCUUUAAGCUCGACGACG-5′ (SEQ ID NO: 504) MYC-739 Target:5′-ATATCTGGAAGAAATTCGAGCTGCTGC-3′ (SEQ ID NO: 831)5′-UAUCUGGAAGAAAUUCGAGCUGCUGCC-3′ (SEQ ID NO: 2140)3′-AUAGACCUUCUUUAAGCUCGACGACGG-5′ (SEQ ID NO: 505) MYC-740 Target:5′-TATCTGGAAGAAATTCGAGCTGCTGCC-3′ (SEQ ID NO: 832)5′-AUCUGGAAGAAAUUCGAGCUGCUGCCC-3′ (SEQ ID NO: 2141)3′-UAGACCUUCUUUAAGCUCGACGACGGG-5′ (SEQ ID NO: 506) MYC-741 Target:5′-ATCTGGAAGAAATTCGAGCTGCTGCCC-3′ (SEQ ID NO: 833)5′-UCUGGAAGAAAUUCGAGCUGCUGCCCA-3′ (SEQ ID NO: 2142)3′-AGACCUUCUUUAAGCUCGACGACGGGU-5′ (SEQ ID NO: 507) MYC-742 Target:5′-TCTGGAAGAAATTCGAGCTGCTGCCCA-3′ (SEQ ID NO: 834)5′-CUGGAAGAAAUUCGAGCUGCUGCCCAC-3′ (SEQ ID NO: 2143)3′-GACCUUCUUUAAGCUCGACGACGGGUG-5′ (SEQ ID NO: 508) MYC-743 Target:5′-CTGGAAGAAATTCGAGCTGCTGCCCAC-3′ (SEQ ID NO: 835)5′-CUAGCCGCCGCUCCGGGCUCUGCUCGC-3′ (SEQ ID NO: 2144)3′-GAUCGGCGGCGAGGCCCGAGACGAGCG-5′ (SEQ ID NO: 509) MYC-784 Target:5′-CTAGCCGCCGCTCCGGGCTCTGCTCGC-3′ (SEQ ID NO: 836)5′-UAGCCGCCGCUCCGGGCUCUGCUCGCC-3′ (SEQ ID NO: 2145)3′-AUCGGCGGCGAGGCCCGAGACGAGCGG-5′ (SEQ ID NO: 510) MYC-785 Target:5′-TAGCCGCCGCTCCGGGCTCTGCTCGCC-3′ (SEQ ID NO: 837)5′-AGCCGCCGCUCCGGGCUCUGCUCGCCC-3′ (SEQ ID NO: 2146)3′-UCGGCGGCGAGGCCCGAGACGAGCGGG-5′ (SEQ ID NO: 511) MYC-786 Target:5′-AGCCGCCGCTCCGGGCTCTGCTCGCCC-3′ (SEQ ID NO: 838)5′-GCCGCCGCUCCGGGCUCUGCUCGCCCU-3′ (SEQ ID NO: 2147)3′-CGGCGGCGAGGCCCGAGACGAGCGGGA-5′ (SEQ ID NO: 512) MYC-787 Target:5′-GCCGCCGCTCCGGGCTCTGCTCGCCCT-3′ (SEQ ID NO: 839)5′-CCGCCGCUCCGGGCUCUGCUCGCCCUC-3′ (SEQ ID NO: 2148)3′-GGCGGCGAGGCCCGAGACGAGCGGGAG-5′ (SEQ ID NO: 513) MYC-788 Target:5′-CCGCCGCTCCGGGCTCTGCTCGCCCTC-3′ (SEQ ID NO: 840)5′-UGGGAGGAGACAUGGUGAACCAGAGUU-3′ (SEQ ID NO: 2149)3′-ACCCUCCUCUGUACCACUUGGUCUCAA-5′ (SEQ ID NO: 514) MYC-913 Target:5′-TGGGAGGAGACATGGTGAACCAGAGTT-3′ (SEQ ID NO: 841)5′-GGGAGGAGACAUGGUGAACCAGAGUUU-3′ (SEQ ID NO: 2150)3′-CCCUCCUCUGUACCACUUGGUCUCAAA-5′ (SEQ ID NO: 515) MYC-914 Target:5′-GGGAGGAGACATGGTGAACCAGAGTTT-3′ (SEQ ID NO: 842)5′-GGAGGAGACAUGGUGAACCAGAGUUUC-3′ (SEQ ID NO: 2151)3′-CCUCCUCUGUACCACUUGGUCUCAAAG-5′ (SEQ ID NO: 516) MYC-915 Target:5′-GGAGGAGACATGGTGAACCAGAGTTTC-3′ (SEQ ID NO: 843)5′-GAGGAGACAUGGUGAACCAGAGUUUCA-3′ (SEQ ID NO: 2152)3′-CUCCUCUGUACCACUUGGUCUCAAAGU-5′ (SEQ ID NO: 517) MYC-916 Target:5′-GAGGAGACATGGTGAACCAGAGTTTCA-3′ (SEQ ID NO: 844)5′-AGGAGACAUGGUGAACCAGAGUUUCAU-3′ (SEQ ID NO: 2153)3′-UCCUCUGUACCACUUGGUCUCAAAGUA-5′ (SEQ ID NO: 518) MYC-917 Target:5′-AGGAGACATGGTGAACCAGAGTTTCAT-3′ (SEQ ID NO: 845)5′-CGGACGACGAGACCUUCAUCAAAAACA-3′ (SEQ ID NO: 2154)3′-GCCUGCUGCUCUGGAAGUAGUUUUUGU-5′ (SEQ ID NO: 519) MYC-952 Target:5′-CGGACGACGAGACCTTCATCAAAAACA-3′ (SEQ ID NO: 846)5′-GGACGACGAGACCUUCAUCAAAAACAU-3′ (SEQ ID NO: 2155)3′-CCUGCUGCUCUGGAAGUAGUUUUUGUA-5′ (SEQ ID NO: 520) MYC-953 Target:5′-GGACGACGAGACCTTCATCAAAAACAT-3′ (SEQ ID NO: 847)5′-AAAACAUCAUCAUCCAGGACUGUAUGU-3′ (SEQ ID NO: 2156)3′-UUUUGUAGUAGUAGGUCCUGACAUACA-5′ (SEQ ID NO: 521) MYC-973 Target:5′-AAAACATCATCATCCAGGACTGTATGT-3′ (SEQ ID NO: 848)5′-AAACAUCAUCAUCCAGGACUGUAUGUG-3′ (SEQ ID NO: 2157)3′-UUUGUAGUAGUAGGUCCUGACAUACAC-5′ (SEQ ID NO: 522) MYC-974 Target:5′-AAACATCATCATCCAGGACTGTATGTG-3′ (SEQ ID NO: 849)5′-AACAUCAUCAUCCAGGACUGUAUGUGG-3′ (SEQ ID NO: 2158)3′-UUGUAGUAGUAGGUCCUGACAUACACC-5′ (SEQ ID NO: 523) MYC-975 Target:5′-AACATCATCATCCAGGACTGTATGTGG-3′ (SEQ ID NO: 850)5′-ACAUCAUCAUCCAGGACUGUAUGUGGA-3′ (SEQ ID NO: 2159)3′-UGUAGUAGUAGGUCCUGACAUACACCU-5′ (SEQ ID NO: 524) MYC-976 Target:5′-ACATCATCATCCAGGACTGTATGTGGA-3′ (SEQ ID NO: 851)5′-CAUCAUCAUCCAGGACUGUAUGUGGAG-3′ (SEQ ID NO: 2160)3′-GUAGUAGUAGGUCCUGACAUACACCUC-5′ (SEQ ID NO: 525) MYC-977 Target:5′-CATCATCATCCAGGACTGTATGTGGAG-3′ (SEQ ID NO: 852)5′-AUCAUCAUCCAGGACUGUAUGUGGAGC-3′ (SEQ ID NO: 2161)3′-UAGUAGUAGGUCCUGACAUACACCUCG-5′ (SEQ ID NO: 526) MYC-978 Target:5′-ATCATCATCCAGGACTGTATGTGGAGC-3′ (SEQ ID NO: 853)5′-UCAUCAUCCAGGACUGUAUGUGGAGCG-3′ (SEQ ID NO: 2162)3′-AGUAGUAGGUCCUGACAUACACCUCGC-5′ (SEQ ID NO: 527) MYC-979 Target:5′-TCATCATCCAGGACTGTATGTGGAGCG-3′ (SEQ ID NO: 854)5′-CAUCAUCCAGGACUGUAUGUGGAGCGG-3′ (SEQ ID NO: 2163)3′-GUAGUAGGUCCUGACAUACACCUCGCC-5′ (SEQ ID NO: 528) MYC-980 Target:5′-CATCATCCAGGACTGTATGTGGAGCGG-3′ (SEQ ID NO: 855)5′-AUCAUCCAGGACUGUAUGUGGAGCGGC-3′ (SEQ ID NO: 2164)3′-UAGUAGGUCCUGACAUACACCUCGCCG-5′ (SEQ ID NO: 529) MYC-981 Target:5′-ATCATCCAGGACTGTATGTGGAGCGGC-3′ (SEQ ID NO: 856)5′-UCAUCCAGGACUGUAUGUGGAGCGGCU-3′ (SEQ ID NO: 2165)3′-AGUAGGUCCUGACAUACACCUCGCCGA-5′ (SEQ ID NO: 530) MYC-982 Target:5′-TCATCCAGGACTGTATGTGGAGCGGCT-3′ (SEQ ID NO: 857)5′-CAUCCAGGACUGUAUGUGGAGCGGCUU-3′ (SEQ ID NO: 2166)3′-GUAGGUCCUGACAUACACCUCGCCGAA-5′ (SEQ ID NO: 531) MYC-983 Target:5′-CATCCAGGACTGTATGTGGAGCGGCTT-3′ (SEQ ID NO: 858)5′-AUCCAGGACUGUAUGUGGAGCGGCUUC-3′ (SEQ ID NO: 2167)3′-UAGGUCCUGACAUACACCUCGCCGAAG-5′ (SEQ ID NO: 532) MYC-984 Target:5′-ATCCAGGACTGTATGTGGAGCGGCTTC-3′ (SEQ ID NO: 859)5′-UCCAGGACUGUAUGUGGAGCGGCUUCU-3′ (SEQ ID NO: 2168)3′-AGGUCCUGACAUACACCUCGCCGAAGA-5′ (SEQ ID NO: 533) MYC-985 Target:5′-TCCAGGACTGTATGTGGAGCGGCTTCT-3′ (SEQ ID NO: 860)5′-CCAGGACUGUAUGUGGAGCGGCUUCUC-3′ (SEQ ID NO: 2169)3′-GGUCCUGACAUACACCUCGCCGAAGAG-5′ (SEQ ID NO: 534) MYC-986 Target:5′-CCAGGACTGTATGTGGAGCGGCTTCTC-3′ (SEQ ID NO: 861)5′-CAGAGAAGCUGGCCUCCUACCAGGCUG-3′ (SEQ ID NO: 2170)3′-GUCUCUUCGACCGGAGGAUGGUCCGAC-5′ (SEQ ID NO: 535) MYC-1033 Target:5′-CAGAGAAGCTGGCCTCCTACCAGGCTG-3′ (SEQ ID NO: 862)5′-AGAGAAGCUGGCCUCCUACCAGGCUGC-3′ (SEQ ID NO: 2171)3′-UCUCUUCGACCGGAGGAUGGUCCGACG-5′ (SEQ ID NO: 536) MYC-1034 Target:5′-AGAGAAGCTGGCCTCCTACCAGGCTGC-3′ (SEQ ID NO: 863)5′-GAGAAGCUGGCCUCCUACCAGGCUGCG-3′ (SEQ ID NO: 2172)3′-CUCUUCGACCGGAGGAUGGUCCGACGC-5′ (SEQ ID NO: 537) MYC-1035 Target:5′-GAGAAGCTGGCCTCCTACCAGGCTGCG-3′ (SEQ ID NO: 864)5′-AGAAGCUGGCCUCCUACCAGGCUGCGC-3′ (SEQ ID NO: 2173)3′-UCUUCGACCGGAGGAUGGUCCGACGCG-5′ (SEQ ID NO: 538) MYC-1036 Target:5′-AGAAGCTGGCCTCCTACCAGGCTGCGC-3′ (SEQ ID NO: 865)5′-GAAGCUGGCCUCCUACCAGGCUGCGCG-3′ (SEQ ID NO: 2174)3′-CUUCGACCGGAGGAUGGUCCGACGCGC-5′ (SEQ ID NO: 539) MYC-1037 Target:5′-GAAGCTGGCCTCCTACCAGGCTGCGCG-3′ (SEQ ID NO: 866)5′-AAGCUGGCCUCCUACCAGGCUGCGCGC-3′ (SEQ ID NO: 2175)3′-UUCGACCGGAGGAUGGUCCGACGCGCG-5′ (SEQ ID NO: 540) MYC-1038 Target:5′-AAGCTGGCCTCCTACCAGGCTGCGCGC-3′ (SEQ ID NO: 867)5′-AGCUGGCCUCCUACCAGGCUGCGCGCA-3′ (SEQ ID NO: 2176)3′-UCGACCGGAGGAUGGUCCGACGCGCGU-5′ (SEQ ID NO: 541) MYC-1039 Target:5′-AGCTGGCCTCCTACCAGGCTGCGCGCA-3′ (SEQ ID NO: 868)5′-GCUGGCCUCCUACCAGGCUGCGCGCAA-3′ (SEQ ID NO: 2177)3′-CGACCGGAGGAUGGUCCGACGCGCGUU-5′ (SEQ ID NO: 542) MYC-1040 Target:5′-GCTGGCCTCCTACCAGGCTGCGCGCAA-3′ (SEQ ID NO: 869)5′-CUGGCCUCCUACCAGGCUGCGCGCAAA-3′ (SEQ ID NO: 2178)3′-GACCGGAGGAUGGUCCGACGCGCGUUU-5′ (SEQ ID NO: 543) MYC-1041 Target:5′-CTGGCCTCCTACCAGGCTGCGCGCAAA-3′ (SEQ ID NO: 870)5′-UGGCCUCCUACCAGGCUGCGCGCAAAG-3′ (SEQ ID NO: 2179)3′-ACCGGAGGAUGGUCCGACGCGCGUUUC-5′ (SEQ ID NO: 544) MYC-1042 Target:5′-TGGCCTCCTACCAGGCTGCGCGCAAAG-3′ (SEQ ID NO: 871)5′-GGCCUCCUACCAGGCUGCGCGCAAAGA-3′ (SEQ ID NO: 2180)3′-CCGGAGGAUGGUCCGACGCGCGUUUCU-5′ (SEQ ID NO: 545) MYC-1043 Target:5′-GGCCTCCTACCAGGCTGCGCGCAAAGA-3′ (SEQ ID NO: 872)5′-GCCUCCUACCAGGCUGCGCGCAAAGAC-3′ (SEQ ID NO: 2181)3′-CGGAGGAUGGUCCGACGCGCGUUUCUG-5′ (SEQ ID NO: 546) MYC-1044 Target:5′-GCCTCCTACCAGGCTGCGCGCAAAGAC-3′ (SEQ ID NO: 873)5′-CCUCCUACCAGGCUGCGCGCAAAGACA-3′ (SEQ ID NO: 2182)3′-GGAGGAUGGUCCGACGCGCGUUUCUGU-5′ (SEQ ID NO: 547) MYC-1045 Target:5′-CCTCCTACCAGGCTGCGCGCAAAGACA-3′ (SEQ ID NO: 874)5′-CUCCUACCAGGCUGCGCGCAAAGACAG-3′ (SEQ ID NO: 2183)3′-GAGGAUGGUCCGACGCGCGUUUCUGUC-5′ (SEQ ID NO: 548) MYC-1046 Target:5′-CTCCTACCAGGCTGCGCGCAAAGACAG-3′ (SEQ ID NO: 875)5′-UCCUACCAGGCUGCGCGCAAAGACAGC-3′ (SEQ ID NO: 2184)3′-AGGAUGGUCCGACGCGCGUUUCUGUCG-5′ (SEQ ID NO: 549) MYC-1047 Target:5′-TCCTACCAGGCTGCGCGCAAAGACAGC-3′ (SEQ ID NO: 876)5′-CCUACCAGGCUGCGCGCAAAGACAGCG-3′ (SEQ ID NO: 2185)3′-GGAUGGUCCGACGCGCGUUUCUGUCGC-5′ (SEQ ID NO: 550) MYC-1048 Target:5′-CCTACCAGGCTGCGCGCAAAGACAGCG-3′ (SEQ ID NO: 877)5′-CUACCAGGCUGCGCGCAAAGACAGCGG-3′ (SEQ ID NO: 2186)3′-GAUGGUCCGACGCGCGUUUCUGUCGCC-5′ (SEQ ID NO: 551) MYC-1049 Target:5′-CTACCAGGCTGCGCGCAAAGACAGCGG-3′ (SEQ ID NO: 878)5′-UACCAGGCUGCGCGCAAAGACAGCGGC-3′ (SEQ ID NO: 2187)3′-AUGGUCCGACGCGCGUUUCUGUCGCCG-5′ (SEQ ID NO: 552) MYC-1050 Target:5′-TACCAGGCTGCGCGCAAAGACAGCGGC-3′ (SEQ ID NO: 879)5′-ACCAGGCUGCGCGCAAAGACAGCGGCA-3′ (SEQ ID NO: 2188)3′-UGGUCCGACGCGCGUUUCUGUCGCCGU-5′ (SEQ ID NO: 553) MYC-1051 Target:5′-ACCAGGCTGCGCGCAAAGACAGCGGCA-3′ (SEQ ID NO: 880)5′-CCAGGCUGCGCGCAAAGACAGCGGCAG-3′ (SEQ ID NO: 2189)3′-GGUCCGACGCGCGUUUCUGUCGCCGUC-5′ (SEQ ID NO: 554) MYC-1052 Target:5′-CCAGGCTGCGCGCAAAGACAGCGGCAG-3′ (SEQ ID NO: 881)5′-CAGGCUGCGCGCAAAGACAGCGGCAGC-3′ (SEQ ID NO: 2190)3′-GUCCGACGCGCGUUUCUGUCGCCGUCG-5′ (SEQ ID NO: 555) MYC-1053 Target:5′-CAGGCTGCGCGCAAAGACAGCGGCAGC-3′ (SEQ ID NO: 882)5′-GCCACAGCGUCUGCUCCACCUCCAGCU-3′ (SEQ ID NO: 2191)3′-CGGUGUCGCAGACGAGGUGGAGGUCGA-5′ (SEQ ID NO: 556) MYC-1096 Target:5′-GCCACAGCGTCTGCTCCACCTCCAGCT-3′ (SEQ ID NO: 883)5′-CCACAGCGUCUGCUCCACCUCCAGCUU-3′ (SEQ ID NO: 2192)3′-GGUGUCGCAGACGAGGUGGAGGUCGAA-5′ (SEQ ID NO: 557) MYC-1097 Target:5′-CCACAGCGTCTGCTCCACCTCCAGCTT-3′ (SEQ ID NO: 884)5′-CACAGCGUCUGCUCCACCUCCAGCUUG-3′ (SEQ ID NO: 2193)3′-GUGUCGCAGACGAGGUGGAGGUCGAAC-5′ (SEQ ID NO: 558) MYC-1098 Target:5′-CACAGCGTCTGCTCCACCTCCAGCTTG-3′ (SEQ ID NO: 885)5′-ACAGCGUCUGCUCCACCUCCAGCUUGU-3′ (SEQ ID NO: 2194)3′-UGUCGCAGACGAGGUGGAGGUCGAACA-5′ (SEQ ID NO: 559) MYC-1099 Target:5′-ACAGCGTCTGCTCCACCTCCAGCTTGT-3′ (SEQ ID NO: 886)5′-CAGCGUCUGCUCCACCUCCAGCUUGUA-3′ (SEQ ID NO: 2195)3′-GUCGCAGACGAGGUGGAGGUCGAACAU-5′ (SEQ ID NO: 560) MYC-1100 Target:5′-CAGCGTCTGCTCCACCTCCAGCTTGTA-3′ (SEQ ID NO: 887)5′-AGCGUCUGCUCCACCUCCAGCUUGUAC-3′ (SEQ ID NO: 2196)3′-UCGCAGACGAGGUGGAGGUCGAACAUG-5′ (SEQ ID NO: 561) MYC-1101 Target:5′-AGCGTCTGCTCCACCTCCAGCTTGTAC-3′ (SEQ ID NO: 888)5′-CUCUCAACGACAGCAGCUCGCCCAAGU-3′ (SEQ ID NO: 2197)3′-GAGAGUUGCUGUCGUCGAGCGGGUUCA-5′ (SEQ ID NO: 562) MYC-1189 Target:5′-CTCTCAACGACAGCAGCTCGCCCAAGT-3′ (SEQ ID NO: 889)5′-UCUCAACGACAGCAGCUCGCCCAAGUC-3′ (SEQ ID NO: 2198)3′-AGAGUUGCUGUCGUCGAGCGGGUUCAG-5′ (SEQ ID NO: 563) MYC-1190 Target:5′-TCTCAACGACAGCAGCTCGCCCAAGTC-3′ (SEQ ID NO: 890)5′-CUCAACGACAGCAGCUCGCCCAAGUCC-3′ (SEQ ID NO: 2199)3′-GAGUUGCUGUCGUCGAGCGGGUUCAGG-5′ (SEQ ID NO: 564) MYC-1191 Target:5′-CTCAACGACAGCAGCTCGCCCAAGTCC-3′ (SEQ ID NO: 891)5′-UCAACGACAGCAGCUCGCCCAAGUCCU-3′ (SEQ ID NO: 2200)3′-AGUUGCUGUCGUCGAGCGGGUUCAGGA-5′ (SEQ ID NO: 565) MYC-1192 Target:5′-TCAACGACAGCAGCTCGCCCAAGTCCT-3′ (SEQ ID NO: 892)5′-CAACGACAGCAGCUCGCCCAAGUCCUG-3′ (SEQ ID NO: 2201)3′-GUUGCUGUCGUCGAGCGGGUUCAGGAC-5′ (SEQ ID NO: 566) MYC-1193 Target:5′-CAACGACAGCAGCTCGCCCAAGTCCTG-3′ (SEQ ID NO: 893)5′-UCCAUGAGGAGACACCGCCCACCACCA-3′ (SEQ ID NO: 2202)3′-AGGUACUCCUCUGUGGCGGGUGGUGGU-5′ (SEQ ID NO: 567) MYC-1315 Target:5′-TCCATGAGGAGACACCGCCCACCACCA-3′ (SEQ ID NO: 894)5′-CCAUGAGGAGACACCGCCCACCACCAG-3′ (SEQ ID NO: 2203)3′-GGUACUCCUCUGUGGCGGGUGGUGGUC-5′ (SEQ ID NO: 568) MYC-1316 Target:5′-CCATGAGGAGACACCGCCCACCACCAG-3′ (SEQ ID NO: 895)5′-CAUGAGGAGACACCGCCCACCACCAGC-3′ (SEQ ID NO: 2204)3′-GUACUCCUCUGUGGCGGGUGGUGGUCG-5′ (SEQ ID NO: 569) MYC-1317 Target:5′-CATGAGGAGACACCGCCCACCACCAGC-3′ (SEQ ID NO: 896)5′-AUGAGGAGACACCGCCCACCACCAGCA-3′ (SEQ ID NO: 2205)3′-UACUCCUCUGUGGCGGGUGGUGGUCGU-5′ (SEQ ID NO: 570) MYC-1318 Target:5′-ATGAGGAGACACCGCCCACCACCAGCA-3′ (SEQ ID NO: 897)5′-UGAGGAGACACCGCCCACCACCAGCAG-3′ (SEQ ID NO: 2206)3′-ACUCCUCUGUGGCGGGUGGUGGUCGUC-5′ (SEQ ID NO: 571) MYC-1319 Target:5′-TGAGGAGACACCGCCCACCACCAGCAG-3′ (SEQ ID NO: 898)5′-GAGGAGACACCGCCCACCACCAGCAGC-3′ (SEQ ID NO: 2207)3′-CUCCUCUGUGGCGGGUGGUGGUCGUCG-5′ (SEQ ID NO: 572) MYC-1320 Target:5′-GAGGAGACACCGCCCACCACCAGCAGC-3′ (SEQ ID NO: 899)5′-AGGAGACACCGCCCACCACCAGCAGCG-3′ (SEQ ID NO: 2208)3′-UCCUCUGUGGCGGGUGGUGGUCGUCGC-5′ (SEQ ID NO: 573) MYC-1321 Target:5′-AGGAGACACCGCCCACCACCAGCAGCG-3′ (SEQ ID NO: 900)5′-GGAGACACCGCCCACCACCAGCAGCGA-3′ (SEQ ID NO: 2209)3′-CCUCUGUGGCGGGUGGUGGUCGUCGCU-5′ (SEQ ID NO: 574) MYC-1322 Target:5′-GGAGACACCGCCCACCACCAGCAGCGA-3′ (SEQ ID NO: 901)5′-GAGACACCGCCCACCACCAGCAGCGAC-3′ (SEQ ID NO: 2210)3′-CUCUGUGGCGGGUGGUGGUCGUCGCUG-5′ (SEQ ID NO: 575) MYC-1323 Target:5′-GAGACACCGCCCACCACCAGCAGCGAC-3′ (SEQ ID NO: 902)5′-AGACACCGCCCACCACCAGCAGCGACU-3′ (SEQ ID NO: 2211)3′-UCUGUGGCGGGUGGUGGUCGUCGCUGA-5′ (SEQ ID NO: 576) MYC-1324 Target:5′-AGACACCGCCCACCACCAGCAGCGACT-3′ (SEQ ID NO: 903)5′-GACACCGCCCACCACCAGCAGCGACUC-3′ (SEQ ID NO: 2212)3′-CUGUGGCGGGUGGUGGUCGUCGCUGAG-5′ (SEQ ID NO: 577) MYC-1325 Target:5′-GACACCGCCCACCACCAGCAGCGACTC-3′ (SEQ ID NO: 904)5′-ACACCGCCCACCACCAGCAGCGACUCU-3′ (SEQ ID NO: 2213)3′-UGUGGCGGGUGGUGGUCGUCGCUGAGA-5′ (SEQ ID NO: 578) MYC-1326 Target:5′-ACACCGCCCACCACCAGCAGCGACTCT-3′ (SEQ ID NO: 905)5′-CACCGCCCACCACCAGCAGCGACUCUG-3′ (SEQ ID NO: 2214)3′-GUGGCGGGUGGUGGUCGUCGCUGAGAC-5′ (SEQ ID NO: 579) MYC-1327 Target:5′-CACCGCCCACCACCAGCAGCGACTCTG-3′ (SEQ ID NO: 906)5′-ACCGCCCACCACCAGCAGCGACUCUGA-3′ (SEQ ID NO: 2215)3′-UGGCGGGUGGUGGUCGUCGCUGAGACU-5′ (SEQ ID NO: 580) MYC-1328 Target:5′-ACCGCCCACCACCAGCAGCGACTCTGA-3′ (SEQ ID NO: 907)5′-CCGCCCACCACCAGCAGCGACUCUGAG-3′ (SEQ ID NO: 2216)3′-GGCGGGUGGUGGUCGUCGCUGAGACUC-5′ (SEQ ID NO: 581) MYC-1329 Target:5′-CCGCCCACCACCAGCAGCGACTCTGAG-3′ (SEQ ID NO: 908)5′-CGCCCACCACCAGCAGCGACUCUGAGG-3′ (SEQ ID NO: 2217)3′-GCGGGUGGUGGUCGUCGCUGAGACUCC-5′ (SEQ ID NO: 582) MYC-1330 Target:5′-CGCCCACCACCAGCAGCGACTCTGAGG-3′ (SEQ ID NO: 909)5′-GCCCACCACCAGCAGCGACUCUGAGGA-3′ (SEQ ID NO: 2218)3′-CGGGUGGUGGUCGUCGCUGAGACUCCU-5′ (SEQ ID NO: 583) MYC-1331 Target:5′-GCCCACCACCAGCAGCGACTCTGAGGA-3′ (SEQ ID NO: 910)5′-CCCACCACCAGCAGCGACUCUGAGGAG-3′ (SEQ ID NO: 2219)3′-GGGUGGUGGUCGUCGCUGAGACUCCUC-5′ (SEQ ID NO: 584) MYC-1332 Target:5′-CCCACCACCAGCAGCGACTCTGAGGAG-3′ (SEQ ID NO: 911)5′-CCACCACCAGCAGCGACUCUGAGGAGG-3′ (SEQ ID NO: 2220)3′-GGUGGUGGUCGUCGCUGAGACUCCUCC-5′ (SEQ ID NO: 585) MYC-1333 Target:5′-CCACCACCAGCAGCGACTCTGAGGAGG-3′ (SEQ ID NO: 912)5′-CACCACCAGCAGCGACUCUGAGGAGGA-3′ (SEQ ID NO: 2221)3′-GUGGUGGUCGUCGCUGAGACUCCUCCU-5′ (SEQ ID NO: 586) MYC-1334 Target:5′-CACCACCAGCAGCGACTCTGAGGAGGA-3′ (SEQ ID NO: 913)5′-AACAAGAAGAUGAGGAAGAAAUCGAUG-3′ (SEQ ID NO: 2222)3′-UUGUUCUUCUACUCCUUCUUUAGCUAC-5′ (SEQ ID NO: 587) MYC-1360 Target:5′-AACAAGAAGATGAGGAAGAAATCGATG-3′ (SEQ ID NO: 914)5′-ACAAGAAGAUGAGGAAGAAAUCGAUGU-3′ (SEQ ID NO: 2223)3′-UGUUCUUCUACUCCUUCUUUAGCUACA-5′ (SEQ ID NO: 588) MYC-1361 Target:5′-ACAAGAAGATGAGGAAGAAATCGATGT-3′ (SEQ ID NO: 915)5′-UGGAGGCCACAGCAAACCUCCUCACAG-3′ (SEQ ID NO: 2224)3′-ACCUCCGGUGUCGUUUGGAGGAGUGUC-5′ (SEQ ID NO: 589) MYC-1448 Target:5′-TGGAGGCCACAGCAAACCTCCTCACAG-3′ (SEQ ID NO: 916)5′-CUCACAGCCCACUGGUCCUCAAGAGGU-3′ (SEQ ID NO: 2225)3′-GAGUGUCGGGUGACCAGGAGUUCUCCA-5′ (SEQ ID NO: 590) MYC-1468 Target:5′-CTCACAGCCCACTGGTCCTCAAGAGGT-3′ (SEQ ID NO: 917)5′-UCACAGCCCACUGGUCCUCAAGAGGUG-3′ (SEQ ID NO: 2226)3′-AGUGUCGGGUGACCAGGAGUUCUCCAC-5′ (SEQ ID NO: 591) MYC-1469 Target:5′-TCACAGCCCACTGGTCCTCAAGAGGTG-3′ (SEQ ID NO: 918)5′-CACAGCCCACUGGUCCUCAAGAGGUGC-3′ (SEQ ID NO: 2227)3′-GUGUCGGGUGACCAGGAGUUCUCCACG-5′ (SEQ ID NO: 592) MYC-1470 Target:5′-CACAGCCCACTGGTCCTCAAGAGGTGC-3′ (SEQ ID NO: 919)5′-ACAGCCCACUGGUCCUCAAGAGGUGCC-3′ (SEQ ID NO: 2228)3′-UGUCGGGUGACCAGGAGUUCUCCACGG-5′ (SEQ ID NO: 593) MYC-1471 Target:5′-ACAGCCCACTGGTCCTCAAGAGGTGCC-3′ (SEQ ID NO: 920)5′-CAGCCCACUGGUCCUCAAGAGGUGCCA-3′ (SEQ ID NO: 2229)3′-GUCGGGUGACCAGGAGUUCUCCACGGU-5′ (SEQ ID NO: 594) MYC-1472 Target:5′-CAGCCCACTGGTCCTCAAGAGGTGCCA-3′ (SEQ ID NO: 921)5′-AGCCCACUGGUCCUCAAGAGGUGCCAC-3′ (SEQ ID NO: 2230)3′-UCGGGUGACCAGGAGUUCUCCACGGUG-5′ (SEQ ID NO: 595) MYC-1473 Target:5′-AGCCCACTGGTCCTCAAGAGGTGCCAC-3′ (SEQ ID NO: 922)5′-GCCCACUGGUCCUCAAGAGGUGCCACG-3′ (SEQ ID NO: 2231)3′-CGGGUGACCAGGAGUUCUCCACGGUGC-5′ (SEQ ID NO: 596) MYC-1474 Target:5′-GCCCACTGGTCCTCAAGAGGTGCCACG-3′ (SEQ ID NO: 923)5′-CCCACUGGUCCUCAAGAGGUGCCACGU-3′ (SEQ ID NO: 2232)3′-GGGUGACCAGGAGUUCUCCACGGUGCA-5′ (SEQ ID NO: 597) MYC-1475 Target:5′-CCCACTGGTCCTCAAGAGGTGCCACGT-3′ (SEQ ID NO: 924)5′-CCACUGGUCCUCAAGAGGUGCCACGUC-3′ (SEQ ID NO: 2233)3′-GGUGACCAGGAGUUCUCCACGGUGCAG-5′ (SEQ ID NO: 598) MYC-1476 Target:5′-CCACTGGTCCTCAAGAGGTGCCACGTC-3′ (SEQ ID NO: 925)5′-CACUGGUCCUCAAGAGGUGCCACGUCU-3′ (SEQ ID NO: 2234)3′-GUGACCAGGAGUUCUCCACGGUGCAGA-5′ (SEQ ID NO: 599) MYC-1477 Target:5′-CACTGGTCCTCAAGAGGTGCCACGTCT-3′ (SEQ ID NO: 926)5′-ACUGGUCCUCAAGAGGUGCCACGUCUC-3′ (SEQ ID NO: 2235)3′-UGACCAGGAGUUCUCCACGGUGCAGAG-5′ (SEQ ID NO: 600) MYC-1478 Target:5′-ACTGGTCCTCAAGAGGTGCCACGTCTC-3′ (SEQ ID NO: 927)5′-CUGGUCCUCAAGAGGUGCCACGUCUCC-3′ (SEQ ID NO: 2236)3′-GACCAGGAGUUCUCCACGGUGCAGAGG-5′ (SEQ ID NO: 601) MYC-1479 Target:5′-CTGGTCCTCAAGAGGTGCCACGTCTCC-3′ (SEQ ID NO: 928)5′-UGGUCCUCAAGAGGUGCCACGUCUCCA-3′ (SEQ ID NO: 2237)3′-ACCAGGAGUUCUCCACGGUGCAGAGGU-5′ (SEQ ID NO: 602) MYC-1480 Target:5′-TGGTCCTCAAGAGGTGCCACGTCTCCA-3′ (SEQ ID NO: 929)5′-GGUCCUCAAGAGGUGCCACGUCUCCAC-3′ (SEQ ID NO: 2238)3′-CCAGGAGUUCUCCACGGUGCAGAGGUG-5′ (SEQ ID NO: 603) MYC-1481 Target:5′-GGTCCTCAAGAGGTGCCACGTCTCCAC-3′ (SEQ ID NO: 930)5′-GUCCUCAAGAGGUGCCACGUCUCCACA-3′ (SEQ ID NO: 2239)3′-CAGGAGUUCUCCACGGUGCAGAGGUGU-5′ (SEQ ID NO: 604) MYC-1482 Target:5′-GTCCTCAAGAGGTGCCACGTCTCCACA-3′ (SEQ ID NO: 931)5′-UCCUCAAGAGGUGCCACGUCUCCACAC-3′ (SEQ ID NO: 2240)3′-AGGAGUUCUCCACGGUGCAGAGGUGUG-5′ (SEQ ID NO: 605) MYC-1483 Target:5′-TCCTCAAGAGGTGCCACGTCTCCACAC-3′ (SEQ ID NO: 932)5′-GGAGCUUUUUUGCCCUGCGUGACCAGA-3′ (SEQ ID NO: 2241)3′-CCUCGAAAAAACGGGACGCACUGGUCU-5′ (SEQ ID NO: 606) MYC-1711 Target:5′-GGAGCTTTTTTGCCCTGCGTGACCAGA-3′ (SEQ ID NO: 933)5′-GAGCUUUUUUGCCCUGCGUGACCAGAU-3′ (SEQ ID NO: 2242)3′-CUCGAAAAAACGGGACGCACUGGUCUA-5′ (SEQ ID NO: 607) MYC-1712 Target:5′-GAGCTTTTTTGCCCTGCGTGACCAGAT-3′ (SEQ ID NO: 934)5′-AGCUUUUUUGCCCUGCGUGACCAGAUC-3′ (SEQ ID NO: 2243)3′-UCGAAAAAACGGGACGCACUGGUCUAG-5′ (SEQ ID NO: 608) MYC-1713 Target:5′-AGCTTTTTTGCCCTGCGTGACCAGATC-3′ (SEQ ID NO: 935)5′-GCUUUUUUGCCCUGCGUGACCAGAUCC-3′ (SEQ ID NO: 2244)3′-CGAAAAAACGGGACGCACUGGUCUAGG-5′ (SEQ ID NO: 609) MYC-1714 Target:5′-GCTTTTTTGCCCTGCGTGACCAGATCC-3′ (SEQ ID NO: 936)5′-CUUUUUUGCCCUGCGUGACCAGAUCCC-3′ (SEQ ID NO: 2245)3′-GAAAAAACGGGACGCACUGGUCUAGGG-5′ (SEQ ID NO: 610) MYC-1715 Target:5′-CTTTTTTGCCCTGCGTGACCAGATCCC-3′ (SEQ ID NO: 937)5′-UUUUUUGCCCUGCGUGACCAGAUCCCG-3′ (SEQ ID NO: 2246)3′-AAAAAACGGGACGCACUGGUCUAGGGC-5′ (SEQ ID NO: 611) MYC-1716 Target:5′-TTTTTTGCCCTGCGTGACCAGATCCCG-3′ (SEQ ID NO: 938)5′-UUUUUGCCCUGCGUGACCAGAUCCCGG-3′ (SEQ ID NO: 2247)3′-AAAAACGGGACGCACUGGUCUAGGGCC-5′ (SEQ ID NO: 612) MYC-1717 Target:5′-TTTTTGCCCTGCGTGACCAGATCCCGG-3′ (SEQ ID NO: 939)5′-UUUUGCCCUGCGUGACCAGAUCCCGGA-3′ (SEQ ID NO: 2248)3′-AAAACGGGACGCACUGGUCUAGGGCCU-5′ (SEQ ID NO: 613) MYC-1718 Target:5′-TTTTGCCCTGCGTGACCAGATCCCGGA-3′ (SEQ ID NO: 940)5′-UUUGCCCUGCGUGACCAGAUCCCGGAG-3′ (SEQ ID NO: 2249)3′-AAACGGGACGCACUGGUCUAGGGCCUC-5′ (SEQ ID NO: 614) MYC-1719 Target:5′-TTTGCCCTGCGTGACCAGATCCCGGAG-3′ (SEQ ID NO: 941)5′-UUGCCCUGCGUGACCAGAUCCCGGAGU-3′ (SEQ ID NO: 2250)3′-AACGGGACGCACUGGUCUAGGGCCUCA-5′ (SEQ ID NO: 615) MYC-1720 Target:5′-TTGCCCTGCGTGACCAGATCCCGGAGT-3′ (SEQ ID NO: 942)5′-UGCCCUGCGUGACCAGAUCCCGGAGUU-3′ (SEQ ID NO: 2251)3′-ACGGGACGCACUGGUCUAGGGCCUCAA-5′ (SEQ ID NO: 616) MYC-1721 Target:5′-TGCCCTGCGTGACCAGATCCCGGAGTT-3′ (SEQ ID NO: 943)5′-GCGGAAACGACGAGAACAGUUGAAACA-3′ (SEQ ID NO: 2252)3′-CGCCUUUGCUGCUCUUGUCAACUUUGU-5′ (SEQ ID NO: 617) MYC-1856 Target:5′-GCGGAAACGACGAGAACAGTTGAAACA-3′ (SEQ ID NO: 944)5′-CGGAAACGACGAGAACAGUUGAAACAC-3′ (SEQ ID NO: 2253)3′-GCCUUUGCUGCUCUUGUCAACUUUGUG-5′ (SEQ ID NO: 618) MYC-1857 Target:5′-CGGAAACGACGAGAACAGTTGAAACAC-3′ (SEQ ID NO: 945)5′-UCUUUAACAGAUUUGUAUUUAAGAAUU-3′ (SEQ ID NO: 2254)3′-AGAAAUUGUCUAAACAUAAAUUCUUAA-5′ (SEQ ID NO: 619) MYC-2115 Target:5′-TCTTTAACAGATTTGTATTTAAGAATT-3′ (SEQ ID NO: 946)5′-CUUUAACAGAUUUGUAUUUAAGAAUUG-3′ (SEQ ID NO: 2255)3′-GAAAUUGUCUAAACAUAAAUUCUUAAC-5′ (SEQ ID NO: 620) MYC-2116 Target:5′-CTTTAACAGATTTGTATTTAAGAATTG-3′ (SEQ ID NO: 947)5′-UUAAAUGUAAAUAACUUUAAUAAAACG-3′ (SEQ ID NO: 2256)3′-AAUUUACAUUUAUUGAAAUUAUUUUGC-5′ (SEQ ID NO: 621) MYC-2193 Target:5′-TTAAATGTAAATAACTTTAATAAAACG-3′ (SEQ ID NO: 948)5′-UAAAUGUAAAUAACUUUAAUAAAACGU-3′ (SEQ ID NO: 2257)3′-AUUUACAUUUAUUGAAAUUAUUUUGCA-5′ (SEQ ID NO: 622) MYC-2194 Target:5′-TAAATGTAAATAACTTTAATAAAACGT-3′ (SEQ ID NO: 949)5′-AAAUGUAAAUAACUUUAAUAAAACGUU-3′ (SEQ ID NO: 2258)3′-UUUACAUUUAUUGAAAUUAUUUUGCAA-5′ (SEQ ID NO: 623) MYC-2195 Target:5′-AAATGTAAATAACTTTAATAAAACGTT-3′ (SEQ ID NO: 950)5′-AAUGUAAAUAACUUUAAUAAAACGUUU-3′ (SEQ ID NO: 2259)3′-UUACAUUUAUUGAAAUUAUUUUGCAAA-5′ (SEQ ID NO: 624) MYC-2196 Target:5′-AATGTAAATAACTTTAATAAAACGTTT-3′ (SEQ ID NO: 951)5′-AUGUAAAUAACUUUAAUAAAACGUUUA-3′ (SEQ ID NO: 2260)3′-UACAUUUAUUGAAAUUAUUUUGCAAAU-5′ (SEQ ID NO: 625) MYC-2197 Target:5′-ATGTAAATAACTTTAATAAAACGTTTA-3′ (SEQ ID NO: 952)5′-UGUAAAUAACUUUAAUAAAACGUUUAU-3′ (SEQ ID NO: 2261)3′-ACAUUUAUUGAAAUUAUUUUGCAAAUA-5′ (SEQ ID NO: 626) MYC-2198 Target:5′-TGTAAATAACTTTAATAAAACGTTTAT-3′ (SEQ ID NO: 953)5′-GUAAAUAACUUUAAUAAAACGUUUAUA-3′ (SEQ ID NO: 2262)3′-CAUUUAUUGAAAUUAUUUUGCAAAUAU-5′ (SEQ ID NO: 627) MYC-2199 Target:5′-GTAAATAACTTTAATAAAACGTTTATA-3′ (SEQ ID NO: 954)5′-UAAAUAACUUUAAUAAAACGUUUAUAG-3′ (SEQ ID NO: 2263)3′-AUUUAUUGAAAUUAUUUUGCAAAUAUC-5′ (SEQ ID NO: 628) MYC-2200 Target:5′-TAAATAACTTTAATAAAACGTTTATAG-3′ (SEQ ID NO: 955)5′-AAAUAACUUUAAUAAAACGUUUAUAGC-3′ (SEQ ID NO: 2264)3′-UUUAUUGAAAUUAUUUUGCAAAUAUCG-5′ (SEQ ID NO: 629) MYC-2201 Target:5′-AAATAACTTTAATAAAACGTTTATAGC-3′ (SEQ ID NO: 956)5′-AAUAACUUUAAUAAAACGUUUAUAGCA-3′ (SEQ ID NO: 2265)3′-UUAUUGAAAUUAUUUUGCAAAUAUCGU-5′ (SEQ ID NO: 630) MYC-2202 Target:5′-AATAACTTTAATAAAACGTTTATAGCA-3′ (SEQ ID NO: 957)5′-AUAACUUUAAUAAAACGUUUAUAGCAG-3′ (SEQ ID NO: 2266)3′-UAUUGAAAUUAUUUUGCAAAUAUCGUC-5′ (SEQ ID NO: 631) MYC-2203 Target:5′-ATAACTTTAATAAAACGTTTATAGCAG-3′ (SEQ ID NO: 958)5′-UAACUUUAAUAAAACGUUUAUAGCAGU-3′ (SEQ ID NO: 2267)3′-AUUGAAAUUAUUUUGCAAAUAUCGUCA-5′ (SEQ ID NO: 632) MYC-2204 Target:5′-TAACTTTAATAAAACGTTTATAGCAGT-3′ (SEQ ID NO: 959)5′-AACUUUAAUAAAACGUUUAUAGCAGUU-3′ (SEQ ID NO: 2268)3′-UUGAAAUUAUUUUGCAAAUAUCGUCAA-5′ (SEQ ID NO: 633) MYC-2205 Target:5′-AACTTTAATAAAACGTTTATAGCAGTT-3′ (SEQ ID NO: 960)5′-GCUUUUUAAAGUUGAUUUUUUUCUAUU-3′ (SEQ ID NO: 2269)3′-CGAAAAAUUUCAACUAAAAAAAGAUAA-5′ (SEQ ID NO: 634) MYC-2313 Target:5′-GCTTTTTAAAGTTGATTTTTTTCTATT-3′ (SEQ ID NO: 961)5′-CUUUUUAAAGUUGAUUUUUUUCUAUUG-3′ (SEQ ID NO: 2270)3′-GAAAAAUUUCAACUAAAAAAAGAUAAC-5′ (SEQ ID NO: 635) MYC-2314 Target:5′-CTTTTTAAAGTTGATTTTTTTCTATTG-3′ (SEQ ID NO: 962)5′-UUUUUAAAGUUGAUUUUUUUCUAUUGU-3′ (SEQ ID NO: 2271)3′-AAAAAUUUCAACUAAAAAAAGAUAACA-5′ (SEQ ID NO: 636) MYC-2315 Target:5′-TTTTTAAAGTTGATTTTTTTCTATTGT-3′ (SEQ ID NO: 963)5′-UUUUAAAGUUGAUUUUUUUCUAUUGUU-3′ (SEQ ID NO: 2272)3′-AAAAUUUCAACUAAAAAAAGAUAACAA-5′ (SEQ ID NO: 637) MYC-2316 Target:5′-TTTTAAAGTTGATTTTTTTCTATTGTT-3′ (SEQ ID NO: 964)5′-UUUAAAGUUGAUUUUUUUCUAUUGUUU-3′ (SEQ ID NO: 2273)3′-AAAUUUCAACUAAAAAAAGAUAACAAA-5′ (SEQ ID NO: 638) MYC-2317 Target:5′-TTTAAAGTTGATTTTTTTCTATTGTTT-3′ (SEQ ID NO: 965)5′-UUAAAGUUGAUUUUUUUCUAUUGUUUU-3′ (SEQ ID NO: 2274)3′-AAUUUCAACUAAAAAAAGAUAACAAAA-5′ (SEQ ID NO: 639) MYC-2318 Target:5′-TTAAAGTTGATTTTTTTCTATTGTTTT-3′ (SEQ ID NO: 966)5′-UAAAGUUGAUUUUUUUCUAUUGUUUUU-3′ (SEQ ID NO: 2275)3′-AUUUCAACUAAAAAAAGAUAACAAAAA-5′ (SEQ ID NO: 640) MYC-2319 Target:5′-TAAAGTTGATTTTTTTCTATTGTTTTT-3′ (SEQ ID NO: 967)5′-AAAGUUGAUUUUUUUCUAUUGUUUUUA-3′ (SEQ ID NO: 2276)3′-UUUCAACUAAAAAAAGAUAACAAAAAU-5′ (SEQ ID NO: 641) MYC-2320 Target:5′-AAAGTTGATTTTTTTCTATTGTTTTTA-3′ (SEQ ID NO: 968)5′-AAGUUGAUUUUUUUCUAUUGUUUUUAG-3′ (SEQ ID NO: 2277)3′-UUCAACUAAAAAAAGAUAACAAAAAUC-5′ (SEQ ID NO: 642) MYC-2321 Target:5′-AAGTTGATTTTTTTCTATTGTTTTTAG-3′ (SEQ ID NO: 969)5′-AGUUGAUUUUUUUCUAUUGUUUUUAGA-3′ (SEQ ID NO: 2278)3′-UCAACUAAAAAAAGAUAACAAAAAUCU-5′ (SEQ ID NO: 643) MYC-2322 Target:5′-AGTTGATTTTTTTCTATTGTTTTTAGA-3′ (SEQ ID NO: 970)5′-GUUGAUUUUUUUCUAUUGUUUUUAGAA-3′ (SEQ ID NO: 2279)3′-CAACUAAAAAAAGAUAACAAAAAUCUU-5′ (SEQ ID NO: 644) MYC-2323 Target:5′-GTTGATTTTTTTCTATTGTTTTTAGAA-3′ (SEQ ID NO: 971)5′-UUGAUUUUUUUCUAUUGUUUUUAGAAA-3′ (SEQ ID NO: 2280)3′-AACUAAAAAAAGAUAACAAAAAUCUUU-5′ (SEQ ID NO: 645) MYC-2324 Target:5′-TTGATTTTTTTCTATTGTTTTTAGAAA-3′ (SEQ ID NO: 972)5′-UGAUUUUUUUCUAUUGUUUUUAGAAAA-3′ (SEQ ID NO: 2281)3′-ACUAAAAAAAGAUAACAAAAAUCUUUU-5′ (SEQ ID NO: 646) MYC-2325 Target:5′-TGATTTTTTTCTATTGTTTTTAGAAAA-3′ (SEQ ID NO: 973)5′-GAUUUUUUUCUAUUGUUUUUAGAAAAA-3′ (SEQ ID NO: 2282)3′-CUAAAAAAAGAUAACAAAAAUCUUUUU-5′ (SEQ ID NO: 647) MYC-2326 Target:5′-GATTTTTTTCTATTGTTTTTAGAAAAA-3′ (SEQ ID NO: 974)5′-AUUUUUUUCUAUUGUUUUUAGAAAAAA-3′ (SEQ ID NO: 2283)3′-UAAAAAAAGAUAACAAAAAUCUUUUUU-5′ (SEQ ID NO: 648) MYC-2327 Target:5′-ATTTTTTTCTATTGTTTTTAGAAAAAA-3′ (SEQ ID NO: 975)5′-UUUUUUUCUAUUGUUUUUAGAAAAAAU-3′ (SEQ ID NO: 2284)3′-AAAAAAAGAUAACAAAAAUCUUUUUUA-5′ (SEQ ID NO: 649) MYC-2328 Target:5′-TTTTTTTCTATTGTTTTTAGAAAAAAT-3′ (SEQ ID NO: 976)5′-UUUUUUCUAUUGUUUUUAGAAAAAAUA-3′ (SEQ ID NO: 2285)3′-AAAAAAGAUAACAAAAAUCUUUUUUAU-5′ (SEQ ID NO: 650) MYC-2329 Target:5′-TTTTTTCTATTGTTTTTAGAAAAAATA-3′ (SEQ ID NO: 977)5′-UUUUUCUAUUGUUUUUAGAAAAAAUAA-3′ (SEQ ID NO: 2286)3′-AAAAAGAUAACAAAAAUCUUUUUUAUU-5′ (SEQ ID NO: 651) MYC-2330 Target:5′-TTTTTCTATTGTTTTTAGAAAAAATAA-3′ (SEQ ID NO: 978)5′-UUUUCUAUUGUUUUUAGAAAAAAUAAA-3′ (SEQ ID NO: 2287)3′-AAAAGAUAACAAAAAUCUUUUUUAUUU-5′ (SEQ ID NO: 652) MYC-2331 Target:5′-TTTTCTATTGTTTTTAGAAAAAATAAA-3′ (SEQ ID NO: 979)5′-UUUCUAUUGUUUUUAGAAAAAAUAAAA-3′ (SEQ ID NO: 2288)3′-AAAGAUAACAAAAAUCUUUUUUAUUUU-5′ (SEQ ID NO: 653) MYC-2332 Target:5′-TTTCTATTGTTTTTAGAAAAAATAAAA-3′ (SEQ ID NO: 980)5′-UUCUAUUGUUUUUAGAAAAAAUAAAAU-3′ (SEQ ID NO: 2289)3′-AAGAUAACAAAAAUCUUUUUUAUUUUA-5′ (SEQ ID NO: 654) MYC-2333 Target:5′-TTCTATTGTTTTTAGAAAAAATAAAAT-3′ (SEQ ID NO: 981)

TABLE 8 DsiRNA Component 19 Nucleotide Target Sequences In MYC mRNAMYC-94 19 nt Target #1: 5′-CGAGAAGGGCAGGGCUUCU-3′ (SEQ ID NO: 2290)MYC-94 19 nt Target #2: 5′-UCGAGAAGGGCAGGGCUUC-3′ (SEQ ID NO: 2617)MYC-94 19 nt Target #3: 5′-CUCGAGAAGGGCAGGGCUU-3′ (SEQ ID NO: 2944)MYC-178 19 nt Target #1: 5′-GCUUUAUCUAACUCGCUGU-3′ (SEQ ID NO: 2291)MYC-178 19 nt Target #2: 5′-GGCUUUAUCUAACUCGCUG-3′ (SEQ ID NO: 2618)MYC-178 19 nt Target #3: 5′-GGGCUUUAUCUAACUCGCU-3′ (SEQ ID NO: 2945)MYC-365 19 nt Target #1: 5′-CCCUUGCCGCAUCCACGAA-3′ (SEQ ID NO: 2292)MYC-365 19 nt Target #2: 5′-ACCCUUGCCGCAUCCACGA-3′ (SEQ ID NO: 2619)MYC-365 19 nt Target #3: 5′-AACCCUUGCCGCAUCCACG-3′ (SEQ ID NO: 2946)MYC-370 19 nt Target #1: 5′-GCCGCAUCCACGAAACUUU-3′ (SEQ ID NO: 2293)MYC-370 19 nt Target #2: 5′-UGCCGCAUCCACGAAACUU-3′ (SEQ ID NO: 2620)MYC-370 19 nt Target #3: 5′-UUGCCGCAUCCACGAAACU-3′ (SEQ ID NO: 2947)MYC-376 19 nt Target #1: 5′-UCCACGAAACUUUGCCCAU-3′ (SEQ ID NO: 2294)MYC-376 19 nt Target #2: 5′-AUCCACGAAACUUUGCCCA-3′ (SEQ ID NO: 2621)MYC-376 19 nt Target #3: 5′-CAUCCACGAAACUUUGCCC-3′ (SEQ ID NO: 2948)MYC-403 19 nt Target #1: 5′-GCGGGCACUUUGCACUGGA-3′ (SEQ ID NO: 2295)MYC-403 19 nt Target #2: 5′-GGCGGGCACUUUGCACUGG-3′ (SEQ ID NO: 2622)MYC-403 19 nt Target #3: 5′-GGGCGGGCACUUUGCACUG-3′ (SEQ ID NO: 2949)MYC-409 19 nt Target #1: 5′-ACUUUGCACUGGAACUUAC-3′ (SEQ ID NO: 2296)MYC-409 19 nt Target #2: 5′-CACUUUGCACUGGAACUUA-3′ (SEQ ID NO: 2623)MYC-409 19 nt Target #3: 5′-GCACUUUGCACUGGAACUU-3′ (SEQ ID NO: 2950)MYC-417 19 nt Target #1: 5′-CUGGAACUUACAACACCCG-3′ (SEQ ID NO: 2297)MYC-417 19 nt Target #2: 5′-ACUGGAACUUACAACACCC-3′ (SEQ ID NO: 2624)MYC-417 19 nt Target #3: 5′-CACUGGAACUUACAACACC-3′ (SEQ ID NO: 2951)MYC-535 19 nt Target #1: 5′-GCAGCUGCUUAGACGCUGG-3′ (SEQ ID NO: 2298)MYC-535 19 nt Target #2: 5′-UGCAGCUGCUUAGACGCUG-3′ (SEQ ID NO: 2625)MYC-535 19 nt Target #3: 5′-UUGCAGCUGCUUAGACGCU-3′ (SEQ ID NO: 2952)MYC-541 19 nt Target #1: 5′-GCUUAGACGCUGGAUUUUU-3′ (SEQ ID NO: 2299)MYC-541 19 nt Target #2: 5′-UGCUUAGACGCUGGAUUUU-3′ (SEQ ID NO: 2626)MYC-541 19 nt Target #3: 5′-CUGCUUAGACGCUGGAUUU-3′ (SEQ ID NO: 2953)MYC-548 19 nt Target #1: 5′-CGCUGGAUUUUUUUCGGGU-3′ (SEQ ID NO: 2300)MYC-548 19 nt Target #2: 5′-ACGCUGGAUUUUUUUCGGG-3′ (SEQ ID NO: 2627)MYC-548 19 nt Target #3: 5′-GACGCUGGAUUUUUUUCGG-3′ (SEQ ID NO: 2954)MYC-553 19 nt Target #1: 5′-GAUUUUUUUCGGGUAGUGG-3′ (SEQ ID NO: 2301)MYC-553 19 nt Target #2: 5′-GGAUUUUUUUCGGGUAGUG-3′ (SEQ ID NO: 2628)MYC-553 19 nt Target #3: 5′-UGGAUUUUUUUCGGGUAGU-3′ (SEQ ID NO: 2955)MYC-562 19 nt Target #1: 5′-CGGGUAGUGGAAAACCAGC-3′ (SEQ ID NO: 2302)MYC-562 19 nt Target #2: 5′-UCGGGUAGUGGAAAACCAG-3′ (SEQ ID NO: 2629)MYC-562 19 nt Target #3: 5′-UUCGGGUAGUGGAAAACCA-3′ (SEQ ID NO: 2956)MYC-601 19 nt Target #1: 5′-CUCAACGUUAGCUUCACCA-3′ (SEQ ID NO: 2303)MYC-601 19 nt Target #2: 5′-CCUCAACGUUAGCUUCACC-3′ (SEQ ID NO: 2630)MYC-601 19 nt Target #3: 5′-CCCUCAACGUUAGCUUCAC-3′ (SEQ ID NO: 2957)MYC-607 19 nt Target #1: 5′-GUUAGCUUCACCAACAGGA-3′ (SEQ ID NO: 2304)MYC-607 19 nt Target #2: 5′-CGUUAGCUUCACCAACAGG-3′ (SEQ ID NO: 2631)MYC-607 19 nt Target #3: 5′-ACGUUAGCUUCACCAACAG-3′ (SEQ ID NO: 2958)MYC-643 19 nt Target #1: 5′-GACUCGGUGCAGCCGUAUU-3′ (SEQ ID NO: 2305)MYC-643 19 nt Target #2: 5′-CGACUCGGUGCAGCCGUAU-3′ (SEQ ID NO: 2632)MYC-643 19 nt Target #3: 5′-ACGACUCGGUGCAGCCGUA-3′ (SEQ ID NO: 2959)MYC-651 19 nt Target #1: 5′-GCAGCCGUAUUUCUACUGC-3′ (SEQ ID NO: 2306)MYC-651 19 nt Target #2: 5′-UGCAGCCGUAUUUCUACUG-3′ (SEQ ID NO: 2633)MYC-651 19 nt Target #3: 5′-GUGCAGCCGUAUUUCUACU-3′ (SEQ ID NO: 2960)MYC-676 19 nt Target #1: 5′-GAGGAGAACUUCUACCAGC-3′ (SEQ ID NO: 2307)MYC-676 19 nt Target #2: 5′-GGAGGAGAACUUCUACCAG-3′ (SEQ ID NO: 2634)MYC-676 19 nt Target #3: 5′-AGGAGGAGAACUUCUACCA-3′ (SEQ ID NO: 2961)MYC-731 19 nt Target #1: 5′-GCGAGGAUAUCUGGAAGAA-3′ (SEQ ID NO: 2308)MYC-731 19 nt Target #2: 5′-AGCGAGGAUAUCUGGAAGA-3′ (SEQ ID NO: 2635)MYC-731 19 nt Target #3: 5′-CAGCGAGGAUAUCUGGAAG-3′ (SEQ ID NO: 2962)MYC-816 19 nt Target #1: 5′-CGUUGCGGUCACACCCUUC-3′ (SEQ ID NO: 2309)MYC-816 19 nt Target #2: 5′-ACGUUGCGGUCACACCCUU-3′ (SEQ ID NO: 2636)MYC-816 19 nt Target #3: 5′-UACGUUGCGGUCACACCCU-3′ (SEQ ID NO: 2963)MYC-920 19 nt Target #1: 5′-ACAUGGUGAACCAGAGUUU-3′ (SEQ ID NO: 2310)MYC-920 19 nt Target #2: 5′-GACAUGGUGAACCAGAGUU-3′ (SEQ ID NO: 2637)MYC-920 19 nt Target #3: 5′-AGACAUGGUGAACCAGAGU-3′ (SEQ ID NO: 2964)MYC-949 19 nt Target #1: 5′-CCGGACGACGAGACCUUCA-3′ (SEQ ID NO: 2311)MYC-949 19 nt Target #2: 5′-CCCGGACGACGAGACCUUC-3′ (SEQ ID NO: 2638)MYC-949 19 nt Target #3: 5′-ACCCGGACGACGAGACCUU-3′ (SEQ ID NO: 2965)MYC-958 19 nt Target #1: 5′-GAGACCUUCAUCAAAAACA-3′ (SEQ ID NO: 2312)MYC-958 19 nt Target #2: 5′-CGAGACCUUCAUCAAAAAC-3′ (SEQ ID NO: 2639)MYC-958 19 nt Target #3: 5′-ACGAGACCUUCAUCAAAAA-3′ (SEQ ID NO: 2966)MYC-970 19 nt Target #1: 5′-AAAAACAUCAUCAUCCAGG-3′ (SEQ ID NO: 2313)MYC-970 19 nt Target #2: 5′-CAAAAACAUCAUCAUCCAG-3′ (SEQ ID NO: 2640)MYC-970 19 nt Target #3: 5′-UCAAAAACAUCAUCAUCCA-3′ (SEQ ID NO: 2967)MYC-987 19 nt Target #1: 5′-GGACUGUAUGUGGAGCGGC-3′ (SEQ ID NO: 2314)MYC-987 19 nt Target #2: 5′-AGGACUGUAUGUGGAGCGG-3′ (SEQ ID NO: 2641)MYC-987 19 nt Target #3: 5′-CAGGACUGUAUGUGGAGCG-3′ (SEQ ID NO: 2968)MYC-1104 19 nt Target #1: 5′-CUGCUCCACCUCCAGCUUG-3′ (SEQ ID NO: 2315)MYC-1104 19 nt Target #2: 5′-UCUGCUCCACCUCCAGCUU-3′ (SEQ ID NO: 2642)MYC-1104 19 nt Target #3: 5′-GUCUGCUCCACCUCCAGCU-3′ (SEQ ID NO: 2969)MYC-1111 19 nt Target #1: 5′-ACCUCCAGCUUGUACCUGC-3′ (SEQ ID NO: 2316)MYC-1111 19 nt Target #2: 5′-CACCUCCAGCUUGUACCUG-3′ (SEQ ID NO: 2643)MYC-1111 19 nt Target #3: 5′-CCACCUCCAGCUUGUACCU-3′ (SEQ ID NO: 2970)MYC-1116 19 nt Target #1: 5′-CAGCUUGUACCUGCAGGAU-3′ (SEQ ID NO: 2317)MYC-1116 19 nt Target #2: 5′-CCAGCUUGUACCUGCAGGA-3′ (SEQ ID NO: 2644)MYC-1116 19 nt Target #3: 5′-UCCAGCUUGUACCUGCAGG-3′ (SEQ ID NO: 2971)MYC-1210 19 nt Target #1: 5′-AAGUCCUGCGCCUCGCAAG-3′ (SEQ ID NO: 2318)MYC-1210 19 nt Target #2: 5′-CAAGUCCUGCGCCUCGCAA-3′ (SEQ ID NO: 2645)MYC-1210 19 nt Target #3: 5′-CCAAGUCCUGCGCCUCGCA-3′ (SEQ ID NO: 2972)MYC-1340 19 nt Target #1: 5′-GCAGCGACUCUGAGGAGGA-3′ (SEQ ID NO: 2319)MYC-1340 19 nt Target #2: 5′-AGCAGCGACUCUGAGGAGG-3′ (SEQ ID NO: 2646)MYC-1340 19 nt Target #3: 5′-CAGCAGCGACUCUGAGGAG-3′ (SEQ ID NO: 2973)MYC-1346 19 nt Target #1: 5′-ACUCUGAGGAGGAACAAGA-3′ (SEQ ID NO: 2320)MYC-1346 19 nt Target #2: 5′-GACUCUGAGGAGGAACAAG-3′ (SEQ ID NO: 2647)MYC-1346 19 nt Target #3: 5′-CGACUCUGAGGAGGAACAA-3′ (SEQ ID NO: 2974)MYC-1351 19 nt Target #1: 5′-GAGGAGGAACAAGAAGAUG-3′ (SEQ ID NO: 2321)MYC-1351 19 nt Target #2: 5′-UGAGGAGGAACAAGAAGAU-3′ (SEQ ID NO: 2648)MYC-1351 19 nt Target #3: 5′-CUGAGGAGGAACAAGAAGA-3′ (SEQ ID NO: 2975)MYC-1358 19 nt Target #1: 5′-AACAAGAAGAUGAGGAAGA-3′ (SEQ ID NO: 2322)MYC-1358 19 nt Target #2: 5′-GAACAAGAAGAUGAGGAAG-3′ (SEQ ID NO: 2649)MYC-1358 19 nt Target #3: 5′-GGAACAAGAAGAUGAGGAA-3′ (SEQ ID NO: 2976)MYC-1364 19 nt Target #1: 5′-AAGAUGAGGAAGAAAUCGA-3′ (SEQ ID NO: 2323)MYC-1364 19 nt Target #2: 5′-GAAGAUGAGGAAGAAAUCG-3′ (SEQ ID NO: 2650)MYC-1364 19 nt Target #3: 5′-AGAAGAUGAGGAAGAAAUC-3′ (SEQ ID NO: 2977)MYC-1370 19 nt Target #1: 5′-AGGAAGAAAUCGAUGUUGU-3′ (SEQ ID NO: 2324)MYC-1370 19 nt Target #2: 5′-GAGGAAGAAAUCGAUGUUG-3′ (SEQ ID NO: 2651)MYC-1370 19 nt Target #3: 5′-UGAGGAAGAAAUCGAUGUU-3′ (SEQ ID NO: 2978)MYC-1376 19 nt Target #1: 5′-AAAUCGAUGUUGUUUCUGU-3′ (SEQ ID NO: 2325)MYC-1376 19 nt Target #2: 5′-GAAAUCGAUGUUGUUUCUG-3′ (SEQ ID NO: 2652)MYC-1376 19 nt Target #3: 5′-AGAAAUCGAUGUUGUUUCU-3′ (SEQ ID NO: 2979)MYC-1382 19 nt Target #1: 5′-AUGUUGUUUCUGUGGAAAA-3′ (SEQ ID NO: 2326)MYC-1382 19 nt Target #2: 5′-GAUGUUGUUUCUGUGGAAA-3′ (SEQ ID NO: 2653)MYC-1382 19 nt Target #3: 5′-CGAUGUUGUUUCUGUGGAA-3′ (SEQ ID NO: 2980)MYC-1401 19 nt Target #1: 5′-GAGGCAGGCUCCUGGCAAA-3′ (SEQ ID NO: 2327)MYC-1401 19 nt Target #2: 5′-AGAGGCAGGCUCCUGGCAA-3′ (SEQ ID NO: 2654)MYC-1401 19 nt Target #3: 5′-AAGAGGCAGGCUCCUGGCA-3′ (SEQ ID NO: 2981)MYC-1406 19 nt Target #1: 5′-AGGCUCCUGGCAAAAGGUC-3′ (SEQ ID NO: 2328)MYC-1406 19 nt Target #2: 5′-CAGGCUCCUGGCAAAAGGU-3′ (SEQ ID NO: 2655)MYC-1406 19 nt Target #3: 5′-GCAGGCUCCUGGCAAAAGG-3′ (SEQ ID NO: 2982)MYC-1411 19 nt Target #1: 5′-CCUGGCAAAAGGUCAGAGU-3′ (SEQ ID NO: 2329)MYC-1411 19 nt Target #2: 5′-UCCUGGCAAAAGGUCAGAG-3′ (SEQ ID NO: 2656)MYC-1411 19 nt Target #3: 5′-CUCCUGGCAAAAGGUCAGA-3′ (SEQ ID NO: 2983)MYC-1416 19 nt Target #1: 5′-CAAAAGGUCAGAGUCUGGA-3′ (SEQ ID NO: 2330)MYC-1416 19 nt Target #2: 5′-GCAAAAGGUCAGAGUCUGG-3′ (SEQ ID NO: 2657)MYC-1416 19 nt Target #3: 5′-GGCAAAAGGUCAGAGUCUG-3′ (SEQ ID NO: 2984)MYC-1421 19 nt Target #1: 5′-GGUCAGAGUCUGGAUCACC-3′ (SEQ ID NO: 2331)MYC-1421 19 nt Target #2: 5′-AGGUCAGAGUCUGGAUCAC-3′ (SEQ ID NO: 2658)MYC-1421 19 nt Target #3: 5′-AAGGUCAGAGUCUGGAUCA-3′ (SEQ ID NO: 2985)MYC-1457 19 nt Target #1: 5′-GCAAACCUCCUCACAGCCC-3′ (SEQ ID NO: 2332)MYC-1457 19 nt Target #2: 5′-AGCAAACCUCCUCACAGCC-3′ (SEQ ID NO: 2659)MYC-1457 19 nt Target #3: 5′-CAGCAAACCUCCUCACAGC-3′ (SEQ ID NO: 2986)MYC-1465 19 nt Target #1: 5′-CCUCACAGCCCACUGGUCC-3′ (SEQ ID NO: 2333)MYC-1465 19 nt Target #2: 5′-UCCUCACAGCCCACUGGUC-3′ (SEQ ID NO: 2660)MYC-1465 19 nt Target #3: 5′-CUCCUCACAGCCCACUGGU-3′ (SEQ ID NO: 2987)MYC-1531 19 nt Target #1: 5′-CCCUCCACUCGGAAGGACU-3′ (SEQ ID NO: 2334)MYC-1531 19 nt Target #2: 5′-UCCCUCCACUCGGAAGGAC-3′ (SEQ ID NO: 2661)MYC-1531 19 nt Target #3: 5′-CUCCCUCCACUCGGAAGGA-3′ (SEQ ID NO: 2988)MYC-1538 19 nt Target #1: 5′-CUCGGAAGGACUAUCCUGC-3′ (SEQ ID NO: 2335)MYC-1538 19 nt Target #2: 5′-ACUCGGAAGGACUAUCCUG-3′ (SEQ ID NO: 2662)MYC-1538 19 nt Target #3: 5′-CACUCGGAAGGACUAUCCU-3′ (SEQ ID NO: 2989)MYC-1550 19 nt Target #1: 5′-AUCCUGCUGCCAAGAGGGU-3′ (SEQ ID NO: 2336)MYC-1550 19 nt Target #2: 5′-UAUCCUGCUGCCAAGAGGG-3′ (SEQ ID NO: 2663)MYC-1550 19 nt Target #3: 5′-CUAUCCUGCUGCCAAGAGG-3′ (SEQ ID NO: 2990)MYC-1555 19 nt Target #1: 5′-GCUGCCAAGAGGGUCAAGU-3′ (SEQ ID NO: 2337)MYC-1555 19 nt Target #2: 5′-UGCUGCCAAGAGGGUCAAG-3′ (SEQ ID NO: 2664)MYC-1555 19 nt Target #3: 5′-CUGCUGCCAAGAGGGUCAA-3′ (SEQ ID NO: 2991)MYC-1560 19 nt Target #1: 5′-CAAGAGGGUCAAGUUGGAC-3′ (SEQ ID NO: 2338)MYC-1560 19 nt Target #2: 5′-CCAAGAGGGUCAAGUUGGA-3′ (SEQ ID NO: 2665)MYC-1560 19 nt Target #3: 5′-GCCAAGAGGGUCAAGUUGG-3′ (SEQ ID NO: 2992)MYC-1565 19 nt Target #1: 5′-GGGUCAAGUUGGACAGUGU-3′ (SEQ ID NO: 2339)MYC-1565 19 nt Target #2: 5′-AGGGUCAAGUUGGACAGUG-3′ (SEQ ID NO: 2666)MYC-1565 19 nt Target #3: 5′-GAGGGUCAAGUUGGACAGU-3′ (SEQ ID NO: 2993)MYC-1570 19 nt Target #1: 5′-AAGUUGGACAGUGUCAGAG-3′ (SEQ ID NO: 2340)MYC-1570 19 nt Target #2: 5′-CAAGUUGGACAGUGUCAGA-3′ (SEQ ID NO: 2667)MYC-1570 19 nt Target #3: 5′-UCAAGUUGGACAGUGUCAG-3′ (SEQ ID NO: 2994)MYC-1575 19 nt Target #1: 5′-GGACAGUGUCAGAGUCCUG-3′ (SEQ ID NO: 2341)MYC-1575 19 nt Target #2: 5′-UGGACAGUGUCAGAGUCCU-3′ (SEQ ID NO: 2668)MYC-1575 19 nt Target #3: 5′-UUGGACAGUGUCAGAGUCC-3′ (SEQ ID NO: 2995)MYC-1584 19 nt Target #1: 5′-CAGAGUCCUGAGACAGAUC-3′ (SEQ ID NO: 2342)MYC-1584 19 nt Target #2: 5′-UCAGAGUCCUGAGACAGAU-3′ (SEQ ID NO: 2669)MYC-1584 19 nt Target #3: 5′-GUCAGAGUCCUGAGACAGA-3′ (SEQ ID NO: 2996)MYC-1593 19 nt Target #1: 5′-GAGACAGAUCAGCAACAAC-3′ (SEQ ID NO: 2343)MYC-1593 19 nt Target #2: 5′-UGAGACAGAUCAGCAACAA-3′ (SEQ ID NO: 2670)MYC-1593 19 nt Target #3: 5′-CUGAGACAGAUCAGCAACA-3′ (SEQ ID NO: 2997)MYC-1599 19 nt Target #1: 5′-GAUCAGCAACAACCGAAAA-3′ (SEQ ID NO: 2344)MYC-1599 19 nt Target #2: 5′-AGAUCAGCAACAACCGAAA-3′ (SEQ ID NO: 2671)MYC-1599 19 nt Target #3: 5′-CAGAUCAGCAACAACCGAA-3′ (SEQ ID NO: 2998)MYC-1634 19 nt Target #1: 5′-CCUCGGACACCGAGGAGAA-3′ (SEQ ID NO: 2345)MYC-1634 19 nt Target #2: 5′-UCCUCGGACACCGAGGAGA-3′ (SEQ ID NO: 2672)MYC-1634 19 nt Target #3: 5′-GUCCUCGGACACCGAGGAG-3′ (SEQ ID NO: 2999)MYC-1639 19 nt Target #1: 5′-GACACCGAGGAGAAUGUCA-3′ (SEQ ID NO: 2346)MYC-1639 19 nt Target #2: 5′-GGACACCGAGGAGAAUGUC-3′ (SEQ ID NO: 2673)MYC-1639 19 nt Target #3: 5′-CGGACACCGAGGAGAAUGU-3′ (SEQ ID NO: 3000)MYC-1687 19 nt Target #1: 5′-CAGAGGAGGAACGAGCUAA-3′ (SEQ ID NO: 2347)MYC-1687 19 nt Target #2: 5′-CCAGAGGAGGAACGAGCUA-3′ (SEQ ID NO: 2674)MYC-1687 19 nt Target #3: 5′-GCCAGAGGAGGAACGAGCU-3′ (SEQ ID NO: 3001)MYC-1693 19 nt Target #1: 5′-AGGAACGAGCUAAAACGGA-3′ (SEQ ID NO: 2348)MYC-1693 19 nt Target #2: 5′-GAGGAACGAGCUAAAACGG-3′ (SEQ ID NO: 2675)MYC-1693 19 nt Target #3: 5′-GGAGGAACGAGCUAAAACG-3′ (SEQ ID NO: 3002)MYC-1698 19 nt Target #1: 5′-CGAGCUAAAACGGAGCUUU-3′ (SEQ ID NO: 2349)MYC-1698 19 nt Target #2: 5′-ACGAGCUAAAACGGAGCUU-3′ (SEQ ID NO: 2676)MYC-1698 19 nt Target #3: 5′-AACGAGCUAAAACGGAGCU-3′ (SEQ ID NO: 3003)MYC-1704 19 nt Target #1: 5′-AAAACGGAGCUUUUUUGCC-3′ (SEQ ID NO: 2350)MYC-1704 19 nt Target #2: 5′-UAAAACGGAGCUUUUUUGC-3′ (SEQ ID NO: 2677)MYC-1704 19 nt Target #3: 5′-CUAAAACGGAGCUUUUUUG-3′ (SEQ ID NO: 3004)MYC-1709 19 nt Target #1: 5′-GGAGCUUUUUUGCCCUGCG-3′ (SEQ ID NO: 2351)MYC-1709 19 nt Target #2: 5′-CGGAGCUUUUUUGCCCUGC-3′ (SEQ ID NO: 2678)MYC-1709 19 nt Target #3: 5′-ACGGAGCUUUUUUGCCCUG-3′ (SEQ ID NO: 3005)MYC-1729 19 nt Target #1: 5′-GACCAGAUCCCGGAGUUGG-3′ (SEQ ID NO: 2352)MYC-1729 19 nt Target #2: 5′-UGACCAGAUCCCGGAGUUG-3′ (SEQ ID NO: 2679)MYC-1729 19 nt Target #3: 5′-GUGACCAGAUCCCGGAGUU-3′ (SEQ ID NO: 3006)MYC-1734 19 nt Target #1: 5′-GAUCCCGGAGUUGGAAAAC-3′ (SEQ ID NO: 2353)MYC-1734 19 nt Target #2: 5′-AGAUCCCGGAGUUGGAAAA-3′ (SEQ ID NO: 2680)MYC-1734 19 nt Target #3: 5′-CAGAUCCCGGAGUUGGAAA-3′ (SEQ ID NO: 3007)MYC-1739 19 nt Target #1: 5′-CGGAGUUGGAAAACAAUGA-3′ (SEQ ID NO: 2354)MYC-1739 19 nt Target #2: 5′-CCGGAGUUGGAAAACAAUG-3′ (SEQ ID NO: 2681)MYC-1739 19 nt Target #3: 5′-CCCGGAGUUGGAAAACAAU-3′ (SEQ ID NO: 3008)MYC-1769 19 nt Target #1: 5′-AGGUAGUUAUCCUUAAAAA-3′ (SEQ ID NO: 2355)MYC-1769 19 nt Target #2: 5′-AAGGUAGUUAUCCUUAAAA-3′ (SEQ ID NO: 2682)MYC-1769 19 nt Target #3: 5′-CAAGGUAGUUAUCCUUAAA-3′ (SEQ ID NO: 3009)MYC-1774 19 nt Target #1: 5′-GUUAUCCUUAAAAAAGCCA-3′ (SEQ ID NO: 2356)MYC-1774 19 nt Target #2: 5′-AGUUAUCCUUAAAAAAGCC-3′ (SEQ ID NO: 2683)MYC-1774 19 nt Target #3: 5′-UAGUUAUCCUUAAAAAAGC-3′ (SEQ ID NO: 3010)MYC-1779 19 nt Target #1: 5′-CCUUAAAAAAGCCACAGCA-3′ (SEQ ID NO: 2357)MYC-1779 19 nt Target #2: 5′-UCCUUAAAAAAGCCACAGC-3′ (SEQ ID NO: 2684)MYC-1779 19 nt Target #3: 5′-AUCCUUAAAAAAGCCACAG-3′ (SEQ ID NO: 3011)MYC-1784 19 nt Target #1: 5′-AAAAAGCCACAGCAUACAU-3′ (SEQ ID NO: 2358)MYC-1784 19 nt Target #2: 5′-AAAAAAGCCACAGCAUACA-3′ (SEQ ID NO: 2685)MYC-1784 19 nt Target #3: 5′-UAAAAAAGCCACAGCAUAC-3′ (SEQ ID NO: 3012)MYC-1789 19 nt Target #1: 5′-GCCACAGCAUACAUCCUGU-3′ (SEQ ID NO: 2359)MYC-1789 19 nt Target #2: 5′-AGCCACAGCAUACAUCCUG-3′ (SEQ ID NO: 2686)MYC-1789 19 nt Target #3: 5′-AAGCCACAGCAUACAUCCU-3′ (SEQ ID NO: 3013)MYC-1795 19 nt Target #1: 5′-GCAUACAUCCUGUCCGUCC-3′ (SEQ ID NO: 2360)MYC-1795 19 nt Target #2: 5′-AGCAUACAUCCUGUCCGUC-3′ (SEQ ID NO: 2687)MYC-1795 19 nt Target #3: 5′-CAGCAUACAUCCUGUCCGU-3′ (SEQ ID NO: 3014)MYC-1803 19 nt Target #1: 5′-CCUGUCCGUCCAAGCAGAG-3′ (SEQ ID NO: 2361)MYC-1803 19 nt Target #2: 5′-UCCUGUCCGUCCAAGCAGA-3′ (SEQ ID NO: 2688)MYC-1803 19 nt Target #3: 5′-AUCCUGUCCGUCCAAGCAG-3′ (SEQ ID NO: 3015)MYC-1808 19 nt Target #1: 5′-CCGUCCAAGCAGAGGAGCA-3′ (SEQ ID NO: 2362)MYC-1808 19 nt Target #2: 5′-UCCGUCCAAGCAGAGGAGC-3′ (SEQ ID NO: 2689)MYC-1808 19 nt Target #3: 5′-GUCCGUCCAAGCAGAGGAG-3′ (SEQ ID NO: 3016)MYC-1816 19 nt Target #1: 5′-GCAGAGGAGCAAAAGCUCA-3′ (SEQ ID NO: 2363)MYC-1816 19 nt Target #2: 5′-AGCAGAGGAGCAAAAGCUC-3′ (SEQ ID NO: 2690)MYC-1816 19 nt Target #3: 5′-AAGCAGAGGAGCAAAAGCU-3′ (SEQ ID NO: 3017)MYC-1823 19 nt Target #1: 5′-AGCAAAAGCUCAUUUCUGA-3′ (SEQ ID NO: 2364)MYC-1823 19 nt Target #2: 5′-GAGCAAAAGCUCAUUUCUG-3′ (SEQ ID NO: 2691)MYC-1823 19 nt Target #3: 5′-GGAGCAAAAGCUCAUUUCU-3′ (SEQ ID NO: 3018)MYC-1828 19 nt Target #1: 5′-AAGCUCAUUUCUGAAGAGG-3′ (SEQ ID NO: 2365)MYC-1828 19 nt Target #2: 5′-AAAGCUCAUUUCUGAAGAG-3′ (SEQ ID NO: 2692)MYC-1828 19 nt Target #3: 5′-AAAAGCUCAUUUCUGAAGA-3′ (SEQ ID NO: 3019)MYC-1834 19 nt Target #1: 5′-AUUUCUGAAGAGGACUUGU-3′ (SEQ ID NO: 2366)MYC-1834 19 nt Target #2: 5′-CAUUUCUGAAGAGGACUUG-3′ (SEQ ID NO: 2693)MYC-1834 19 nt Target #3: 5′-UCAUUUCUGAAGAGGACUU-3′ (SEQ ID NO: 3020)MYC-1840 19 nt Target #1: 5′-GAAGAGGACUUGUUGCGGA-3′ (SEQ ID NO: 2367)MYC-1840 19 nt Target #2: 5′-UGAAGAGGACUUGUUGCGG-3′ (SEQ ID NO: 2694)MYC-1840 19 nt Target #3: 5′-CUGAAGAGGACUUGUUGCG-3′ (SEQ ID NO: 3021)MYC-1845 19 nt Target #1: 5′-GGACUUGUUGCGGAAACGA-3′ (SEQ ID NO: 2368)MYC-1845 19 nt Target #2: 5′-AGGACUUGUUGCGGAAACG-3′ (SEQ ID NO: 2695)MYC-1845 19 nt Target #3: 5′-GAGGACUUGUUGCGGAAAC-3′ (SEQ ID NO: 3022)MYC-1850 19 nt Target #1: 5′-UGUUGCGGAAACGACGAGA-3′ (SEQ ID NO: 2369)MYC-1850 19 nt Target #2: 5′-UUGUUGCGGAAACGACGAG-3′ (SEQ ID NO: 2696)MYC-1850 19 nt Target #3: 5′-CUUGUUGCGGAAACGACGA-3′ (SEQ ID NO: 3023)MYC-1855 19 nt Target #1: 5′-CGGAAACGACGAGAACAGU-3′ (SEQ ID NO: 2370)MYC-1855 19 nt Target #2: 5′-GCGGAAACGACGAGAACAG-3′ (SEQ ID NO: 2697)MYC-1855 19 nt Target #3: 5′-UGCGGAAACGACGAGAACA-3′ (SEQ ID NO: 3024)MYC-1882 19 nt Target #1: 5′-AAACUUGAACAGCUACGGA-3′ (SEQ ID NO: 2371)MYC-1882 19 nt Target #2: 5′-CAAACUUGAACAGCUACGG-3′ (SEQ ID NO: 2698)MYC-1882 19 nt Target #3: 5′-ACAAACUUGAACAGCUACG-3′ (SEQ ID NO: 3025)MYC-1888 19 nt Target #1: 5′-GAACAGCUACGGAACUCUU-3′ (SEQ ID NO: 2372)MYC-1888 19 nt Target #2: 5′-UGAACAGCUACGGAACUCU-3′ (SEQ ID NO: 2699)MYC-1888 19 nt Target #3: 5′-UUGAACAGCUACGGAACUC-3′ (SEQ ID NO: 3026)MYC-1893 19 nt Target #1: 5′-GCUACGGAACUCUUGUGCG-3′ (SEQ ID NO: 2373)MYC-1893 19 nt Target #2: 5′-AGCUACGGAACUCUUGUGC-3′ (SEQ ID NO: 2700)MYC-1893 19 nt Target #3: 5′-CAGCUACGGAACUCUUGUG-3′ (SEQ ID NO: 3027)MYC-1900 19 nt Target #1: 5′-AACUCUUGUGCGUAAGGAA-3′ (SEQ ID NO: 2374)MYC-1900 19 nt Target #2: 5′-GAACUCUUGUGCGUAAGGA-3′ (SEQ ID NO: 2701)MYC-1900 19 nt Target #3: 5′-GGAACUCUUGUGCGUAAGG-3′ (SEQ ID NO: 3028)MYC-1906 19 nt Target #1: 5′-UGUGCGUAAGGAAAAGUAA-3′ (SEQ ID NO: 2375)MYC-1906 19 nt Target #2: 5′-UUGUGCGUAAGGAAAAGUA-3′ (SEQ ID NO: 2702)MYC-1906 19 nt Target #3: 5′-CUUGUGCGUAAGGAAAAGU-3′ (SEQ ID NO: 3029)MYC-1911 19 nt Target #1: 5′-GUAAGGAAAAGUAAGGAAA-3′ (SEQ ID NO: 2376)MYC-1911 19 nt Target #2: 5′-CGUAAGGAAAAGUAAGGAA-3′ (SEQ ID NO: 2703)MYC-1911 19 nt Target #3: 5′-GCGUAAGGAAAAGUAAGGA-3′ (SEQ ID NO: 3030)MYC-1921 19 nt Target #1: 5′-GUAAGGAAAACGAUUCCUU-3′ (SEQ ID NO: 2377)MYC-1921 19 nt Target #2: 5′-AGUAAGGAAAACGAUUCCU-3′ (SEQ ID NO: 2704)MYC-1921 19 nt Target #3: 5′-AAGUAAGGAAAACGAUUCC-3′ (SEQ ID NO: 3031)MYC-1926 19 nt Target #1: 5′-GAAAACGAUUCCUUCUAAC-3′ (SEQ ID NO: 2378)MYC-1926 19 nt Target #2: 5′-GGAAAACGAUUCCUUCUAA-3′ (SEQ ID NO: 2705)MYC-1926 19 nt Target #3: 5′-AGGAAAACGAUUCCUUCUA-3′ (SEQ ID NO: 3032)MYC-1931 19 nt Target #1: 5′-CGAUUCCUUCUAACAGAAA-3′ (SEQ ID NO: 2379)MYC-1931 19 nt Target #2: 5′-ACGAUUCCUUCUAACAGAA-3′ (SEQ ID NO: 2706)MYC-1931 19 nt Target #3: 5′-AACGAUUCCUUCUAACAGA-3′ (SEQ ID NO: 3033)MYC-1937 19 nt Target #1: 5′-CUUCUAACAGAAAUGUCCU-3′ (SEQ ID NO: 2380)MYC-1937 19 nt Target #2: 5′-CCUUCUAACAGAAAUGUCC-3′ (SEQ ID NO: 2707)MYC-1937 19 nt Target #3: 5′-UCCUUCUAACAGAAAUGUC-3′ (SEQ ID NO: 3034)MYC-1944 19 nt Target #1: 5′-CAGAAAUGUCCUGAGCAAU-3′ (SEQ ID NO: 2381)MYC-1944 19 nt Target #2: 5′-ACAGAAAUGUCCUGAGCAA-3′ (SEQ ID NO: 2708)MYC-1944 19 nt Target #3: 5′-AACAGAAAUGUCCUGAGCA-3′ (SEQ ID NO: 3035)MYC-1953 19 nt Target #1: 5′-CCUGAGCAAUCACCUAUGA-3′ (SEQ ID NO: 2382)MYC-1953 19 nt Target #2: 5′-UCCUGAGCAAUCACCUAUG-3′ (SEQ ID NO: 2709)MYC-1953 19 nt Target #3: 5′-GUCCUGAGCAAUCACCUAU-3′ (SEQ ID NO: 3036)MYC-1959 19 nt Target #1: 5′-CAAUCACCUAUGAACUUGU-3′ (SEQ ID NO: 2383)MYC-1959 19 nt Target #2: 5′-GCAAUCACCUAUGAACUUG-3′ (SEQ ID NO: 2710)MYC-1959 19 nt Target #3: 5′-AGCAAUCACCUAUGAACUU-3′ (SEQ ID NO: 3037)MYC-1965 19 nt Target #1: 5′-CCUAUGAACUUGUUUCAAA-3′ (SEQ ID NO: 2384)MYC-1965 19 nt Target #2: 5′-ACCUAUGAACUUGUUUCAA-3′ (SEQ ID NO: 2711)MYC-1965 19 nt Target #3: 5′-CACCUAUGAACUUGUUUCA-3′ (SEQ ID NO: 3038)MYC-1970 19 nt Target #1: 5′-GAACUUGUUUCAAAUGCAU-3′ (SEQ ID NO: 2385)MYC-1970 19 nt Target #2: 5′-UGAACUUGUUUCAAAUGCA-3′ (SEQ ID NO: 2712)MYC-1970 19 nt Target #3: 5′-AUGAACUUGUUUCAAAUGC-3′ (SEQ ID NO: 3039)MYC-1976 19 nt Target #1: 5′-GUUUCAAAUGCAUGAUCAA-3′ (SEQ ID NO: 2386)MYC-1976 19 nt Target #2: 5′-UGUUUCAAAUGCAUGAUCA-3′ (SEQ ID NO: 2713)MYC-1976 19 nt Target #3: 5′-UUGUUUCAAAUGCAUGAUC-3′ (SEQ ID NO: 3040)MYC-1981 19 nt Target #1: 5′-AAAUGCAUGAUCAAAUGCA-3′ (SEQ ID NO: 2387)MYC-1981 19 nt Target #2: 5′-CAAAUGCAUGAUCAAAUGC-3′ (SEQ ID NO: 2714)MYC-1981 19 nt Target #3: 5′-UCAAAUGCAUGAUCAAAUG-3′ (SEQ ID NO: 3041)MYC-1989 19 nt Target #1: 5′-GAUCAAAUGCAACCUCACA-3′ (SEQ ID NO: 2388)MYC-1989 19 nt Target #2: 5′-UGAUCAAAUGCAACCUCAC-3′ (SEQ ID NO: 2715)MYC-1989 19 nt Target #3: 5′-AUGAUCAAAUGCAACCUCA-3′ (SEQ ID NO: 3042)MYC-1994 19 nt Target #1: 5′-AAUGCAACCUCACAACCUU-3′ (SEQ ID NO: 2389)MYC-1994 19 nt Target #2: 5′-AAAUGCAACCUCACAACCU-3′ (SEQ ID NO: 2716)MYC-1994 19 nt Target #3: 5′-CAAAUGCAACCUCACAACC-3′ (SEQ ID NO: 3043)MYC-2001 19 nt Target #1: 5′-CCUCACAACCUUGGCUGAG-3′ (SEQ ID NO: 2390)MYC-2001 19 nt Target #2: 5′-ACCUCACAACCUUGGCUGA-3′ (SEQ ID NO: 2717)MYC-2001 19 nt Target #3: 5′-AACCUCACAACCUUGGCUG-3′ (SEQ ID NO: 3044)MYC-2006 19 nt Target #1: 5′-CAACCUUGGCUGAGUCUUG-3′ (SEQ ID NO: 2391)MYC-2006 19 nt Target #2: 5′-ACAACCUUGGCUGAGUCUU-3′ (SEQ ID NO: 2718)MYC-2006 19 nt Target #3: 5′-CACAACCUUGGCUGAGUCU-3′ (SEQ ID NO: 3045)MYC-2013 19 nt Target #1: 5′-GGCUGAGUCUUGAGACUGA-3′ (SEQ ID NO: 2392)MYC-2013 19 nt Target #2: 5′-UGGCUGAGUCUUGAGACUG-3′ (SEQ ID NO: 2719)MYC-2013 19 nt Target #3: 5′-UUGGCUGAGUCUUGAGACU-3′ (SEQ ID NO: 3046)MYC-2019 19 nt Target #1: 5′-GUCUUGAGACUGAAAGAUU-3′ (SEQ ID NO: 2393)MYC-2019 19 nt Target #2: 5′-AGUCUUGAGACUGAAAGAU-3′ (SEQ ID NO: 2720)MYC-2019 19 nt Target #3: 5′-GAGUCUUGAGACUGAAAGA-3′ (SEQ ID NO: 3047)MYC-2026 19 nt Target #1: 5′-GACUGAAAGAUUUAGCCAU-3′ (SEQ ID NO: 2394)MYC-2026 19 nt Target #2: 5′-AGACUGAAAGAUUUAGCCA-3′ (SEQ ID NO: 2721)MYC-2026 19 nt Target #3: 5′-GAGACUGAAAGAUUUAGCC-3′ (SEQ ID NO: 3048)MYC-2031 19 nt Target #1: 5′-AAAGAUUUAGCCAUAAUGU-3′ (SEQ ID NO: 2395)MYC-2031 19 nt Target #2: 5′-GAAAGAUUUAGCCAUAAUG-3′ (SEQ ID NO: 2722)MYC-2031 19 nt Target #3: 5′-UGAAAGAUUUAGCCAUAAU-3′ (SEQ ID NO: 3049)MYC-2040 19 nt Target #1: 5′-GCCAUAAUGUAAACUGCCU-3′ (SEQ ID NO: 2396)MYC-2040 19 nt Target #2: 5′-AGCCAUAAUGUAAACUGCC-3′ (SEQ ID NO: 2723)MYC-2040 19 nt Target #3: 5′-UAGCCAUAAUGUAAACUGC-3′ (SEQ ID NO: 3050)MYC-2048 19 nt Target #1: 5′-GUAAACUGCCUCAAAUUGG-3′ (SEQ ID NO: 2397)MYC-2048 19 nt Target #2: 5′-UGUAAACUGCCUCAAAUUG-3′ (SEQ ID NO: 2724)MYC-2048 19 nt Target #3: 5′-AUGUAAACUGCCUCAAAUU-3′ (SEQ ID NO: 3051)MYC-2054 19 nt Target #1: 5′-UGCCUCAAAUUGGACUUUG-3′ (SEQ ID NO: 2398)MYC-2054 19 nt Target #2: 5′-CUGCCUCAAAUUGGACUUU-3′ (SEQ ID NO: 2725)MYC-2054 19 nt Target #3: 5′-ACUGCCUCAAAUUGGACUU-3′ (SEQ ID NO: 3052)MYC-2059 19 nt Target #1: 5′-CAAAUUGGACUUUGGGCAU-3′ (SEQ ID NO: 2399)MYC-2059 19 nt Target #2: 5′-UCAAAUUGGACUUUGGGCA-3′ (SEQ ID NO: 2726)MYC-2059 19 nt Target #3: 5′-CUCAAAUUGGACUUUGGGC-3′ (SEQ ID NO: 3053)MYC-2066 19 nt Target #1: 5′-GACUUUGGGCAUAAAAGAA-3′ (SEQ ID NO: 2400)MYC-2066 19 nt Target #2: 5′-GGACUUUGGGCAUAAAAGA-3′ (SEQ ID NO: 2727)MYC-2066 19 nt Target #3: 5′-UGGACUUUGGGCAUAAAAG-3′ (SEQ ID NO: 3054)MYC-2073 19 nt Target #1: 5′-GGCAUAAAAGAACUUUUUU-3′ (SEQ ID NO: 2401)MYC-2073 19 nt Target #2: 5′-GGGCAUAAAAGAACUUUUU-3′ (SEQ ID NO: 2728)MYC-2073 19 nt Target #3: 5′-UGGGCAUAAAAGAACUUUU-3′ (SEQ ID NO: 3055)MYC-2078 19 nt Target #1: 5′-AAAAGAACUUUUUUAUGCU-3′ (SEQ ID NO: 2402)MYC-2078 19 nt Target #2: 5′-UAAAAGAACUUUUUUAUGC-3′ (SEQ ID NO: 2729)MYC-2078 19 nt Target #3: 5′-AUAAAAGAACUUUUUUAUG-3′ (SEQ ID NO: 3056)MYC-2083 19 nt Target #1: 5′-AACUUUUUUAUGCUUACCA-3′ (SEQ ID NO: 2403)MYC-2083 19 nt Target #2: 5′-GAACUUUUUUAUGCUUACC-3′ (SEQ ID NO: 2730)MYC-2083 19 nt Target #3: 5′-AGAACUUUUUUAUGCUUAC-3′ (SEQ ID NO: 3057)MYC-2089 19 nt Target #1: 5′-UUUAUGCUUACCAUCUUUU-3′ (SEQ ID NO: 2404)MYC-2089 19 nt Target #2: 5′-UUUUAUGCUUACCAUCUUU-3′ (SEQ ID NO: 2731)MYC-2089 19 nt Target #3: 5′-UUUUUAUGCUUACCAUCUU-3′ (SEQ ID NO: 3058)MYC-2094 19 nt Target #1: 5′-GCUUACCAUCUUUUUUUUU-3′ (SEQ ID NO: 2405)MYC-2094 19 nt Target #2: 5′-UGCUUACCAUCUUUUUUUU-3′ (SEQ ID NO: 2732)MYC-2094 19 nt Target #3: 5′-AUGCUUACCAUCUUUUUUU-3′ (SEQ ID NO: 3059)MYC-2099 19 nt Target #1: 5′-CCAUCUUUUUUUUUUCUUU-3′ (SEQ ID NO: 2406)MYC-2099 19 nt Target #2: 5′-ACCAUCUUUUUUUUUUCUU-3′ (SEQ ID NO: 2733)MYC-2099 19 nt Target #3: 5′-UACCAUCUUUUUUUUUUCU-3′ (SEQ ID NO: 3060)MYC-2105 19 nt Target #1: 5′-UUUUUUUUUCUUUAACAGA-3′ (SEQ ID NO: 2407)MYC-2105 19 nt Target #2: 5′-UUUUUUUUUUCUUUAACAG-3′ (SEQ ID NO: 2734)MYC-2105 19 nt Target #3: 5′-CUUUUUUUUUUCUUUAACA-3′ (SEQ ID NO: 3061)MYC-2114 19 nt Target #1: 5′-CUUUAACAGAUUUGUAUUU-3′ (SEQ ID NO: 2408)MYC-2114 19 nt Target #2: 5′-UCUUUAACAGAUUUGUAUU-3′ (SEQ ID NO: 2735)MYC-2114 19 nt Target #3: 5′-UUCUUUAACAGAUUUGUAU-3′ (SEQ ID NO: 3062)MYC-2120 19 nt Target #1: 5′-CAGAUUUGUAUUUAAGAAU-3′ (SEQ ID NO: 2409)MYC-2120 19 nt Target #2: 5′-ACAGAUUUGUAUUUAAGAA-3′ (SEQ ID NO: 2736)MYC-2120 19 nt Target #3: 5′-AACAGAUUUGUAUUUAAGA-3′ (SEQ ID NO: 3063)MYC-2128 19 nt Target #1: 5′-UAUUUAAGAAUUGUUUUUA-3′ (SEQ ID NO: 2410)MYC-2128 19 nt Target #2: 5′-GUAUUUAAGAAUUGUUUUU-3′ (SEQ ID NO: 2737)MYC-2128 19 nt Target #3: 5′-UGUAUUUAAGAAUUGUUUU-3′ (SEQ ID NO: 3064)MYC-2135 19 nt Target #1: 5′-GAAUUGUUUUUAAAAAAUU-3′ (SEQ ID NO: 2411)MYC-2135 19 nt Target #2: 5′-AGAAUUGUUUUUAAAAAAU-3′ (SEQ ID NO: 2738)MYC-2135 19 nt Target #3: 5′-AAGAAUUGUUUUUAAAAAA-3′ (SEQ ID NO: 3065)MYC-2167 19 nt Target #1: 5′-AAUGUUUCUCUGUAAAUAU-3′ (SEQ ID NO: 2412)MYC-2167 19 nt Target #2: 5′-CAAUGUUUCUCUGUAAAUA-3′ (SEQ ID NO: 2739)MYC-2167 19 nt Target #3: 5′-ACAAUGUUUCUCUGUAAAU-3′ (SEQ ID NO: 3066)MYC-2176 19 nt Target #1: 5′-CUGUAAAUAUUGCCAUUAA-3′ (SEQ ID NO: 2413)MYC-2176 19 nt Target #2: 5′-UCUGUAAAUAUUGCCAUUA-3′ (SEQ ID NO: 2740)MYC-2176 19 nt Target #3: 5′-CUCUGUAAAUAUUGCCAUU-3′ (SEQ ID NO: 3067)MYC-2181 19 nt Target #1: 5′-AAUAUUGCCAUUAAAUGUA-3′ (SEQ ID NO: 2414)MYC-2181 19 nt Target #2: 5′-AAAUAUUGCCAUUAAAUGU-3′ (SEQ ID NO: 2741)MYC-2181 19 nt Target #3: 5′-UAAAUAUUGCCAUUAAAUG-3′ (SEQ ID NO: 3068)MYC-2188 19 nt Target #1: 5′-CCAUUAAAUGUAAAUAACU-3′ (SEQ ID NO: 2415)MYC-2188 19 nt Target #2: 5′-GCCAUUAAAUGUAAAUAAC-3′ (SEQ ID NO: 2742)MYC-2188 19 nt Target #3: 5′-UGCCAUUAAAUGUAAAUAA-3′ (SEQ ID NO: 3069)MYC-2207 19 nt Target #1: 5′-UUAAUAAAACGUUUAUAGC-3′ (SEQ ID NO: 2416)MYC-2207 19 nt Target #2: 5′-UUUAAUAAAACGUUUAUAG-3′ (SEQ ID NO: 2743)MYC-2207 19 nt Target #3: 5′-CUUUAAUAAAACGUUUAUA-3′ (SEQ ID NO: 3070)MYC-2233 19 nt Target #1: 5′-CAGAAUUUCAAUCCUAGUA-3′ (SEQ ID NO: 2417)MYC-2233 19 nt Target #2: 5′-ACAGAAUUUCAAUCCUAGU-3′ (SEQ ID NO: 2744)MYC-2233 19 nt Target #3: 5′-CACAGAAUUUCAAUCCUAG-3′ (SEQ ID NO: 3071)MYC-2260 19 nt Target #1: 5′-CUAGUAUUAUAGGUACUAU-3′ (SEQ ID NO: 2418)MYC-2260 19 nt Target #2: 5′-CCUAGUAUUAUAGGUACUA-3′ (SEQ ID NO: 2745)MYC-2260 19 nt Target #3: 5′-ACCUAGUAUUAUAGGUACU-3′ (SEQ ID NO: 3072)MYC-2267 19 nt Target #1: 5′-UAUAGGUACUAUAAACCCU-3′ (SEQ ID NO: 2419)MYC-2267 19 nt Target #2: 5′-UUAUAGGUACUAUAAACCC-3′ (SEQ ID NO: 2746)MYC-2267 19 nt Target #3: 5′-AUUAUAGGUACUAUAAACC-3′ (SEQ ID NO: 3073)MYC-2274 19 nt Target #1: 5′-ACUAUAAACCCUAAUUUUU-3′ (SEQ ID NO: 2420)MYC-2274 19 nt Target #2: 5′-UACUAUAAACCCUAAUUUU-3′ (SEQ ID NO: 2747)MYC-2274 19 nt Target #3: 5′-GUACUAUAAACCCUAAUUU-3′ (SEQ ID NO: 3074)MYC-2282 19 nt Target #1: 5′-CCCUAAUUUUUUUUAUUUA-3′ (SEQ ID NO: 2421)MYC-2282 19 nt Target #2: 5′-ACCCUAAUUUUUUUUAUUU-3′ (SEQ ID NO: 2748)MYC-2282 19 nt Target #3: 5′-AACCCUAAUUUUUUUUAUU-3′ (SEQ ID NO: 3075)MYC-2287 19 nt Target #1: 5′-AUUUUUUUUAUUUAAGUAC-3′ (SEQ ID NO: 2422)MYC-2287 19 nt Target #2: 5′-AAUUUUUUUUAUUUAAGUA-3′ (SEQ ID NO: 2749)MYC-2287 19 nt Target #3: 5′-UAAUUUUUUUUAUUUAAGU-3′ (SEQ ID NO: 3076)MYC-2295 19 nt Target #1: 5′-UAUUUAAGUACAUUUUGCU-3′ (SEQ ID NO: 2423)MYC-2295 19 nt Target #2: 5′-UUAUUUAAGUACAUUUUGC-3′ (SEQ ID NO: 2750)MYC-2295 19 nt Target #3: 5′-UUUAUUUAAGUACAUUUUG-3′ (SEQ ID NO: 3077)MYC-2300 19 nt Target #1: 5′-AAGUACAUUUUGCUUUUUA-3′ (SEQ ID NO: 2424)MYC-2300 19 nt Target #2: 5′-UAAGUACAUUUUGCUUUUU-3′ (SEQ ID NO: 2751)MYC-2300 19 nt Target #3: 5′-UUAAGUACAUUUUGCUUUU-3′ (SEQ ID NO: 3078)MYC-2306 19 nt Target #1: 5′-AUUUUGCUUUUUAAAGUUG-3′ (SEQ ID NO: 2425)MYC-2306 19 nt Target #2: 5′-CAUUUUGCUUUUUAAAGUU-3′ (SEQ ID NO: 2752)MYC-2306 19 nt Target #3: 5′-ACAUUUUGCUUUUUAAAGU-3′ (SEQ ID NO: 3079)MYC-2312 19 nt Target #1: 5′-CUUUUUAAAGUUGAUUUUU-3′ (SEQ ID NO: 2426)MYC-2312 19 nt Target #2: 5′-GCUUUUUAAAGUUGAUUUU-3′ (SEQ ID NO: 2753)MYC-2312 19 nt Target #3: 5′-UGCUUUUUAAAGUUGAUUU-3′ (SEQ ID NO: 3080)MYC-2334 19 nt Target #1: 5′-UAUUGUUUUUAGAAAAAAU-3′ (SEQ ID NO: 2427)MYC-2334 19 nt Target #2: 5′-CUAUUGUUUUUAGAAAAAA-3′ (SEQ ID NO: 2754)MYC-2334 19 nt Target #3: 5′-UCUAUUGUUUUUAGAAAAA-3′ (SEQ ID NO: 3081)MYC-2339 19 nt Target #1: 5′-UUUUUAGAAAAAAUAAAAU-3′ (SEQ ID NO: 2428)MYC-2339 19 nt Target #2: 5′-GUUUUUAGAAAAAAUAAAA-3′ (SEQ ID NO: 2755)MYC-2339 19 nt Target #3: 5′-UGUUUUUAGAAAAAAUAAA-3′ (SEQ ID NO: 3082)MYC-2347 19 nt Target #1: 5′-AAAAAUAAAAUAACUGGCA-3′ (SEQ ID NO: 2429)MYC-2347 19 nt Target #2: 5′-AAAAAAUAAAAUAACUGGC-3′ (SEQ ID NO: 2756)MYC-2347 19 nt Target #3: 5′-GAAAAAAUAAAAUAACUGG-3′ (SEQ ID NO: 3083)MYC-2355 19 nt Target #1: 5′-AAUAACUGGCAAAUAUAUC-3′ (SEQ ID NO: 2430)MYC-2355 19 nt Target #2: 5′-AAAUAACUGGCAAAUAUAU-3′ (SEQ ID NO: 2757)MYC-2355 19 nt Target #3: 5′-AAAAUAACUGGCAAAUAUA-3′ (SEQ ID NO: 3084)MYC-2364 19 nt Target #1: 5′-CAAAUAUAUCAUUGAGCCA-3′ (SEQ ID NO: 2431)MYC-2364 19 nt Target #2: 5′-GCAAAUAUAUCAUUGAGCC-3′ (SEQ ID NO: 2758)MYC-2364 19 nt Target #3: 5′-GGCAAAUAUAUCAUUGAGC-3′ (SEQ ID NO: 3085)MYC-2371 19 nt Target #1: 5′-AUCAUUGAGCCAAAUCUUA-3′ (SEQ ID NO: 2432)MYC-2371 19 nt Target #2: 5′-UAUCAUUGAGCCAAAUCUU-3′ (SEQ ID NO: 2759)MYC-2371 19 nt Target #3: 5′-AUAUCAUUGAGCCAAAUCU-3′ (SEQ ID NO: 3086)MYC-2377 19 nt Target #1: 5′-GAGCCAAAUCUUAAAAAAA-3′ (SEQ ID NO: 2433)MYC-2377 19 nt Target #2: 5′-UGAGCCAAAUCUUAAAAAA-3′ (SEQ ID NO: 2760)MYC-2377 19 nt Target #3: 5′-UUGAGCCAAAUCUUAAAAA-3′ (SEQ ID NO: 3087)MYC-188 19 nt Target #1: 5′-ACUCGCUGUAGUAAUUCCA-3′ (SEQ ID NO: 2434)MYC-188 19 nt Target #2: 5′-AACUCGCUGUAGUAAUUCC-3′ (SEQ ID NO: 2761)MYC-188 19 nt Target #3: 5′-UAACUCGCUGUAGUAAUUC-3′ (SEQ ID NO: 3088)MYC-189 19 nt Target #1: 5′-CUCGCUGUAGUAAUUCCAG-3′ (SEQ ID NO: 2435)MYC-189 19 nt Target #2: 5′-ACUCGCUGUAGUAAUUCCA-3′ (SEQ ID NO: 2762)MYC-189 19 nt Target #3: 5′-AACUCGCUGUAGUAAUUCC-3′ (SEQ ID NO: 3089)MYC-190 19 nt Target #1: 5′-UCGCUGUAGUAAUUCCAGC-3′ (SEQ ID NO: 2436)MYC-190 19 nt Target #2: 5′-CUCGCUGUAGUAAUUCCAG-3′ (SEQ ID NO: 2763)MYC-190 19 nt Target #3: 5′-ACUCGCUGUAGUAAUUCCA-3′ (SEQ ID NO: 3090)MYC-191 19 nt Target #1: 5′-CGCUGUAGUAAUUCCAGCG-3′ (SEQ ID NO: 2437)MYC-191 19 nt Target #2: 5′-UCGCUGUAGUAAUUCCAGC-3′ (SEQ ID NO: 2764)MYC-191 19 nt Target #3: 5′-CUCGCUGUAGUAAUUCCAG-3′ (SEQ ID NO: 3091)MYC-192 19 nt Target #1: 5′-GCUGUAGUAAUUCCAGCGA-3′ (SEQ ID NO: 2438)MYC-192 19 nt Target #2: 5′-CGCUGUAGUAAUUCCAGCG-3′ (SEQ ID NO: 2765)MYC-192 19 nt Target #3: 5′-UCGCUGUAGUAAUUCCAGC-3′ (SEQ ID NO: 3092)MYC-193 19 nt Target #1: 5′-CUGUAGUAAUUCCAGCGAG-3′ (SEQ ID NO: 2439)MYC-193 19 nt Target #2: 5′-GCUGUAGUAAUUCCAGCGA-3′ (SEQ ID NO: 2766)MYC-193 19 nt Target #3: 5′-CGCUGUAGUAAUUCCAGCG-3′ (SEQ ID NO: 3093)MYC-194 19 nt Target #1: 5′-UGUAGUAAUUCCAGCGAGA-3′ (SEQ ID NO: 2440)MYC-194 19 nt Target #2: 5′-CUGUAGUAAUUCCAGCGAG-3′ (SEQ ID NO: 2767)MYC-194 19 nt Target #3: 5′-GCUGUAGUAAUUCCAGCGA-3′ (SEQ ID NO: 3094)MYC-195 19 nt Target #1: 5′-GUAGUAAUUCCAGCGAGAG-3′ (SEQ ID NO: 2441)MYC-195 19 nt Target #2: 5′-UGUAGUAAUUCCAGCGAGA-3′ (SEQ ID NO: 2768)MYC-195 19 nt Target #3: 5′-CUGUAGUAAUUCCAGCGAG-3′ (SEQ ID NO: 3095)MYC-612 19 nt Target #1: 5′-CUUCACCAACAGGAACUAU-3′ (SEQ ID NO: 2442)MYC-612 19 nt Target #2: 5′-GCUUCACCAACAGGAACUA-3′ (SEQ ID NO: 2769)MYC-612 19 nt Target #3: 5′-AGCUUCACCAACAGGAACU-3′ (SEQ ID NO: 3096)MYC-613 19 nt Target #1: 5′-UUCACCAACAGGAACUAUG-3′ (SEQ ID NO: 2443)MYC-613 19 nt Target #2: 5′-CUUCACCAACAGGAACUAU-3′ (SEQ ID NO: 2770)MYC-613 19 nt Target #3: 5′-GCUUCACCAACAGGAACUA-3′ (SEQ ID NO: 3097)MYC-614 19 nt Target #1: 5′-UCACCAACAGGAACUAUGA-3′ (SEQ ID NO: 2444)MYC-614 19 nt Target #2: 5′-UUCACCAACAGGAACUAUG-3′ (SEQ ID NO: 2771)MYC-614 19 nt Target #3: 5′-CUUCACCAACAGGAACUAU-3′ (SEQ ID NO: 3098)MYC-615 19 nt Target #1: 5′-CACCAACAGGAACUAUGAC-3′ (SEQ ID NO: 2445)MYC-615 19 nt Target #2: 5′-UCACCAACAGGAACUAUGA-3′ (SEQ ID NO: 2772)MYC-615 19 nt Target #3: 5′-UUCACCAACAGGAACUAUG-3′ (SEQ ID NO: 3099)MYC-616 19 nt Target #1: 5′-ACCAACAGGAACUAUGACC-3′ (SEQ ID NO: 2446)MYC-616 19 nt Target #2: 5′-CACCAACAGGAACUAUGAC-3′ (SEQ ID NO: 2773)MYC-616 19 nt Target #3: 5′-UCACCAACAGGAACUAUGA-3′ (SEQ ID NO: 3100)MYC-617 19 nt Target #1: 5′-CCAACAGGAACUAUGACCU-3′ (SEQ ID NO: 2447)MYC-617 19 nt Target #2: 5′-ACCAACAGGAACUAUGACC-3′ (SEQ ID NO: 2774)MYC-617 19 nt Target #3: 5′-CACCAACAGGAACUAUGAC-3′ (SEQ ID NO: 3101)MYC-618 19 nt Target #1: 5′-CAACAGGAACUAUGACCUC-3′ (SEQ ID NO: 2448)MYC-618 19 nt Target #2: 5′-CCAACAGGAACUAUGACCU-3′ (SEQ ID NO: 2775)MYC-618 19 nt Target #3: 5′-ACCAACAGGAACUAUGACC-3′ (SEQ ID NO: 3102)MYC-619 19 nt Target #1: 5′-AACAGGAACUAUGACCUCG-3′ (SEQ ID NO: 2449)MYC-619 19 nt Target #2: 5′-CAACAGGAACUAUGACCUC-3′ (SEQ ID NO: 2776)MYC-619 19 nt Target #3: 5′-CCAACAGGAACUAUGACCU-3′ (SEQ ID NO: 3103)MYC-620 19 nt Target #1: 5′-ACAGGAACUAUGACCUCGA-3′ (SEQ ID NO: 2450)MYC-620 19 nt Target #2: 5′-AACAGGAACUAUGACCUCG-3′ (SEQ ID NO: 2777)MYC-620 19 nt Target #3: 5′-CAACAGGAACUAUGACCUC-3′ (SEQ ID NO: 3104)MYC-621 19 nt Target #1: 5′-CAGGAACUAUGACCUCGAC-3′ (SEQ ID NO: 2451)MYC-621 19 nt Target #2: 5′-ACAGGAACUAUGACCUCGA-3′ (SEQ ID NO: 2778)MYC-621 19 nt Target #3: 5′-AACAGGAACUAUGACCUCG-3′ (SEQ ID NO: 3105)MYC-622 19 nt Target #1: 5′-AGGAACUAUGACCUCGACU-3′ (SEQ ID NO: 2452)MYC-622 19 nt Target #2: 5′-CAGGAACUAUGACCUCGAC-3′ (SEQ ID NO: 2779)MYC-622 19 nt Target #3: 5′-ACAGGAACUAUGACCUCGA-3′ (SEQ ID NO: 3106)MYC-623 19 nt Target #1: 5′-GGAACUAUGACCUCGACUA-3′ (SEQ ID NO: 2453)MYC-623 19 nt Target #2: 5′-AGGAACUAUGACCUCGACU-3′ (SEQ ID NO: 2780)MYC-623 19 nt Target #3: 5′-CAGGAACUAUGACCUCGAC-3′ (SEQ ID NO: 3107)MYC-624 19 nt Target #1: 5′-GAACUAUGACCUCGACUAC-3′ (SEQ ID NO: 2454)MYC-624 19 nt Target #2: 5′-GGAACUAUGACCUCGACUA-3′ (SEQ ID NO: 2781)MYC-624 19 nt Target #3: 5′-AGGAACUAUGACCUCGACU-3′ (SEQ ID NO: 3108)MYC-625 19 nt Target #1: 5′-AACUAUGACCUCGACUACG-3′ (SEQ ID NO: 2455)MYC-625 19 nt Target #2: 5′-GAACUAUGACCUCGACUAC-3′ (SEQ ID NO: 2782)MYC-625 19 nt Target #3: 5′-GGAACUAUGACCUCGACUA-3′ (SEQ ID NO: 3109)MYC-626 19 nt Target #1: 5′-ACUAUGACCUCGACUACGA-3′ (SEQ ID NO: 2456)MYC-626 19 nt Target #2: 5′-AACUAUGACCUCGACUACG-3′ (SEQ ID NO: 2783)MYC-626 19 nt Target #3: 5′-GAACUAUGACCUCGACUAC-3′ (SEQ ID NO: 3110)MYC-627 19 nt Target #1: 5′-CUAUGACCUCGACUACGAC-3′ (SEQ ID NO: 2457)MYC-627 19 nt Target #2: 5′-ACUAUGACCUCGACUACGA-3′ (SEQ ID NO: 2784)MYC-627 19 nt Target #3: 5′-AACUAUGACCUCGACUACG-3′ (SEQ ID NO: 3111)MYC-628 19 nt Target #1: 5′-UAUGACCUCGACUACGACU-3′ (SEQ ID NO: 2458)MYC-628 19 nt Target #2: 5′-CUAUGACCUCGACUACGAC-3′ (SEQ ID NO: 2785)MYC-628 19 nt Target #3: 5′-ACUAUGACCUCGACUACGA-3′ (SEQ ID NO: 3112)MYC-629 19 nt Target #1: 5′-AUGACCUCGACUACGACUC-3′ (SEQ ID NO: 2459)MYC-629 19 nt Target #2: 5′-UAUGACCUCGACUACGACU-3′ (SEQ ID NO: 2786)MYC-629 19 nt Target #3: 5′-CUAUGACCUCGACUACGAC-3′ (SEQ ID NO: 3113)MYC-733 19 nt Target #1: 5′-GAGGAUAUCUGGAAGAAAU-3′ (SEQ ID NO: 2460)MYC-733 19 nt Target #2: 5′-CGAGGAUAUCUGGAAGAAA-3′ (SEQ ID NO: 2787)MYC-733 19 nt Target #3: 5′-GCGAGGAUAUCUGGAAGAA-3′ (SEQ ID NO: 3114)MYC-734 19 nt Target #1: 5′-AGGAUAUCUGGAAGAAAUU-3′ (SEQ ID NO: 2461)MYC-734 19 nt Target #2: 5′-GAGGAUAUCUGGAAGAAAU-3′ (SEQ ID NO: 2788)MYC-734 19 nt Target #3: 5′-CGAGGAUAUCUGGAAGAAA-3′ (SEQ ID NO: 3115)MYC-735 19 nt Target #1: 5′-GGAUAUCUGGAAGAAAUUC-3′ (SEQ ID NO: 2462)MYC-735 19 nt Target #2: 5′-AGGAUAUCUGGAAGAAAUU-3′ (SEQ ID NO: 2789)MYC-735 19 nt Target #3: 5′-GAGGAUAUCUGGAAGAAAU-3′ (SEQ ID NO: 3116)MYC-736 19 nt Target #1: 5′-GAUAUCUGGAAGAAAUUCG-3′ (SEQ ID NO: 2463)MYC-736 19 nt Target #2: 5′-GGAUAUCUGGAAGAAAUUC-3′ (SEQ ID NO: 2790)MYC-736 19 nt Target #3: 5′-AGGAUAUCUGGAAGAAAUU-3′ (SEQ ID NO: 3117)MYC-737 19 nt Target #1: 5′-AUAUCUGGAAGAAAUUCGA-3′ (SEQ ID NO: 2464)MYC-737 19 nt Target #2: 5′-GAUAUCUGGAAGAAAUUCG-3′ (SEQ ID NO: 2791)MYC-737 19 nt Target #3: 5′-GGAUAUCUGGAAGAAAUUC-3′ (SEQ ID NO: 3118)MYC-738 19 nt Target #1: 5′-UAUCUGGAAGAAAUUCGAG-3′ (SEQ ID NO: 2465)MYC-738 19 nt Target #2: 5′-AUAUCUGGAAGAAAUUCGA-3′ (SEQ ID NO: 2792)MYC-738 19 nt Target #3: 5′-GAUAUCUGGAAGAAAUUCG-3′ (SEQ ID NO: 3119)MYC-739 19 nt Target #1: 5′-AUCUGGAAGAAAUUCGAGC-3′ (SEQ ID NO: 2466)MYC-739 19 nt Target #2: 5′-UAUCUGGAAGAAAUUCGAG-3′ (SEQ ID NO: 2793)MYC-739 19 nt Target #3: 5′-AUAUCUGGAAGAAAUUCGA-3′ (SEQ ID NO: 3120)MYC-740 19 nt Target #1: 5′-UCUGGAAGAAAUUCGAGCU-3′ (SEQ ID NO: 2467)MYC-740 19 nt Target #2: 5′-AUCUGGAAGAAAUUCGAGC-3′ (SEQ ID NO: 2794)MYC-740 19 nt Target #3: 5′-UAUCUGGAAGAAAUUCGAG-3′ (SEQ ID NO: 3121)MYC-741 19 nt Target #1: 5′-CUGGAAGAAAUUCGAGCUG-3′ (SEQ ID NO: 2468)MYC-741 19 nt Target #2: 5′-UCUGGAAGAAAUUCGAGCU-3′ (SEQ ID NO: 2795)MYC-741 19 nt Target #3: 5′-AUCUGGAAGAAAUUCGAGC-3′ (SEQ ID NO: 3122)MYC-742 19 nt Target #1: 5′-UGGAAGAAAUUCGAGCUGC-3′ (SEQ ID NO: 2469)MYC-742 19 nt Target #2: 5′-CUGGAAGAAAUUCGAGCUG-3′ (SEQ ID NO: 2796)MYC-742 19 nt Target #3: 5′-UCUGGAAGAAAUUCGAGCU-3′ (SEQ ID NO: 3123)MYC-743 19 nt Target #1: 5′-GGAAGAAAUUCGAGCUGCU-3′ (SEQ ID NO: 2470)MYC-743 19 nt Target #2: 5′-UGGAAGAAAUUCGAGCUGC-3′ (SEQ ID NO: 2797)MYC-743 19 nt Target #3: 5′-CUGGAAGAAAUUCGAGCUG-3′ (SEQ ID NO: 3124)MYC-784 19 nt Target #1: 5′-AGCCGCCGCUCCGGGCUCU-3′ (SEQ ID NO: 2471)MYC-784 19 nt Target #2: 5′-UAGCCGCCGCUCCGGGCUC-3′ (SEQ ID NO: 2798)MYC-784 19 nt Target #3: 5′-CUAGCCGCCGCUCCGGGCU-3′ (SEQ ID NO: 3125)MYC-785 19 nt Target #1: 5′-GCCGCCGCUCCGGGCUCUG-3′ (SEQ ID NO: 2472)MYC-785 19 nt Target #2: 5′-AGCCGCCGCUCCGGGCUCU-3′ (SEQ ID NO: 2799)MYC-785 19 nt Target #3: 5′-UAGCCGCCGCUCCGGGCUC-3′ (SEQ ID NO: 3126)MYC-786 19 nt Target #1: 5′-CCGCCGCUCCGGGCUCUGC-3′ (SEQ ID NO: 2473)MYC-786 19 nt Target #2: 5′-GCCGCCGCUCCGGGCUCUG-3′ (SEQ ID NO: 2800)MYC-786 19 nt Target #3: 5′-AGCCGCCGCUCCGGGCUCU-3′ (SEQ ID NO: 3127)MYC-787 19 nt Target #1: 5′-CGCCGCUCCGGGCUCUGCU-3′ (SEQ ID NO: 2474)MYC-787 19 nt Target #2: 5′-CCGCCGCUCCGGGCUCUGC-3′ (SEQ ID NO: 2801)MYC-787 19 nt Target #3: 5′-GCCGCCGCUCCGGGCUCUG-3′ (SEQ ID NO: 3128)MYC-788 19 nt Target #1: 5′-GCCGCUCCGGGCUCUGCUC-3′ (SEQ ID NO: 2475)MYC-788 19 nt Target #2: 5′-CGCCGCUCCGGGCUCUGCU-3′ (SEQ ID NO: 2802)MYC-788 19 nt Target #3: 5′-CCGCCGCUCCGGGCUCUGC-3′ (SEQ ID NO: 3129)MYC-913 19 nt Target #1: 5′-GGAGGAGACAUGGUGAACC-3′ (SEQ ID NO: 2476)MYC-913 19 nt Target #2: 5′-GGGAGGAGACAUGGUGAAC-3′ (SEQ ID NO: 2803)MYC-913 19 nt Target #3: 5′-UGGGAGGAGACAUGGUGAA-3′ (SEQ ID NO: 3130)MYC-914 19 nt Target #1: 5′-GAGGAGACAUGGUGAACCA-3′ (SEQ ID NO: 2477)MYC-914 19 nt Target #2: 5′-GGAGGAGACAUGGUGAACC-3′ (SEQ ID NO: 2804)MYC-914 19 nt Target #3: 5′-GGGAGGAGACAUGGUGAAC-3′ (SEQ ID NO: 3131)MYC-915 19 nt Target #1: 5′-AGGAGACAUGGUGAACCAG-3′ (SEQ ID NO: 2478)MYC-915 19 nt Target #2: 5′-GAGGAGACAUGGUGAACCA-3′ (SEQ ID NO: 2805)MYC-915 19 nt Target #3: 5′-GGAGGAGACAUGGUGAACC-3′ (SEQ ID NO: 3132)MYC-916 19 nt Target #1: 5′-GGAGACAUGGUGAACCAGA-3′ (SEQ ID NO: 2479)MYC-916 19 nt Target #2: 5′-AGGAGACAUGGUGAACCAG-3′ (SEQ ID NO: 2806)MYC-916 19 nt Target #3: 5′-GAGGAGACAUGGUGAACCA-3′ (SEQ ID NO: 3133)MYC-917 19 nt Target #1: 5′-GAGACAUGGUGAACCAGAG-3′ (SEQ ID NO: 2480)MYC-917 19 nt Target #2: 5′-GGAGACAUGGUGAACCAGA-3′ (SEQ ID NO: 2807)MYC-917 19 nt Target #3: 5′-AGGAGACAUGGUGAACCAG-3′ (SEQ ID NO: 3134)MYC-952 19 nt Target #1: 5′-GACGACGAGACCUUCAUCA-3′ (SEQ ID NO: 2481)MYC-952 19 nt Target #2: 5′-GGACGACGAGACCUUCAUC-3′ (SEQ ID NO: 2808)MYC-952 19 nt Target #3: 5′-CGGACGACGAGACCUUCAU-3′ (SEQ ID NO: 3135)MYC-953 19 nt Target #1: 5′-ACGACGAGACCUUCAUCAA-3′ (SEQ ID NO: 2482)MYC-953 19 nt Target #2: 5′-GACGACGAGACCUUCAUCA-3′ (SEQ ID NO: 2809)MYC-953 19 nt Target #3: 5′-GGACGACGAGACCUUCAUC-3′ (SEQ ID NO: 3136)MYC-973 19 nt Target #1: 5′-AACAUCAUCAUCCAGGACU-3′ (SEQ ID NO: 2483)MYC-973 19 nt Target #2: 5′-AAACAUCAUCAUCCAGGAC-3′ (SEQ ID NO: 2810)MYC-973 19 nt Target #3: 5′-AAAACAUCAUCAUCCAGGA-3′ (SEQ ID NO: 3137)MYC-974 19 nt Target #1: 5′-ACAUCAUCAUCCAGGACUG-3′ (SEQ ID NO: 2484)MYC-974 19 nt Target #2: 5′-AACAUCAUCAUCCAGGACU-3′ (SEQ ID NO: 2811)MYC-974 19 nt Target #3: 5′-AAACAUCAUCAUCCAGGAC-3′ (SEQ ID NO: 3138)MYC-975 19 nt Target #1: 5′-CAUCAUCAUCCAGGACUGU-3′ (SEQ ID NO: 2485)MYC-975 19 nt Target #2: 5′-ACAUCAUCAUCCAGGACUG-3′ (SEQ ID NO: 2812)MYC-975 19 nt Target #3: 5′-AACAUCAUCAUCCAGGACU-3′ (SEQ ID NO: 3139)MYC-976 19 nt Target #1: 5′-AUCAUCAUCCAGGACUGUA-3′ (SEQ ID NO: 2486)MYC-976 19 nt Target #2: 5′-CAUCAUCAUCCAGGACUGU-3′ (SEQ ID NO: 2813)MYC-976 19 nt Target #3: 5′-ACAUCAUCAUCCAGGACUG-3′ (SEQ ID NO: 3140)MYC-977 19 nt Target #1: 5′-UCAUCAUCCAGGACUGUAU-3′ (SEQ ID NO: 2487)MYC-977 19 nt Target #2: 5′-AUCAUCAUCCAGGACUGUA-3′ (SEQ ID NO: 2814)MYC-977 19 nt Target #3: 5′-CAUCAUCAUCCAGGACUGU-3′ (SEQ ID NO: 3141)MYC-978 19 nt Target #1: 5′-CAUCAUCCAGGACUGUAUG-3′ (SEQ ID NO: 2488)MYC-978 19 nt Target #2: 5′-UCAUCAUCCAGGACUGUAU-3′ (SEQ ID NO: 2815)MYC-978 19 nt Target #3: 5′-AUCAUCAUCCAGGACUGUA-3′ (SEQ ID NO: 3142)MYC-979 19 nt Target #1: 5′-AUCAUCCAGGACUGUAUGU-3′ (SEQ ID NO: 2489)MYC-979 19 nt Target #2: 5′-CAUCAUCCAGGACUGUAUG-3′ (SEQ ID NO: 2816)MYC-979 19 nt Target #3: 5′-UCAUCAUCCAGGACUGUAU-3′ (SEQ ID NO: 3143)MYC-980 19 nt Target #1: 5′-UCAUCCAGGACUGUAUGUG-3′ (SEQ ID NO: 2490)MYC-980 19 nt Target #2: 5′-AUCAUCCAGGACUGUAUGU-3′ (SEQ ID NO: 2817)MYC-980 19 nt Target #3: 5′-CAUCAUCCAGGACUGUAUG-3′ (SEQ ID NO: 3144)MYC-981 19 nt Target #1: 5′-CAUCCAGGACUGUAUGUGG-3′ (SEQ ID NO: 2491)MYC-981 19 nt Target #2: 5′-UCAUCCAGGACUGUAUGUG-3′ (SEQ ID NO: 2818)MYC-981 19 nt Target #3: 5′-AUCAUCCAGGACUGUAUGU-3′ (SEQ ID NO: 3145)MYC-982 19 nt Target #1: 5′-AUCCAGGACUGUAUGUGGA-3′ (SEQ ID NO: 2492)MYC-982 19 nt Target #2: 5′-CAUCCAGGACUGUAUGUGG-3′ (SEQ ID NO: 2819)MYC-982 19 nt Target #3: 5′-UCAUCCAGGACUGUAUGUG-3′ (SEQ ID NO: 3146)MYC-983 19 nt Target #1: 5′-UCCAGGACUGUAUGUGGAG-3′ (SEQ ID NO: 2493)MYC-983 19 nt Target #2: 5′-AUCCAGGACUGUAUGUGGA-3′ (SEQ ID NO: 2820)MYC-983 19 nt Target #3: 5′-CAUCCAGGACUGUAUGUGG-3′ (SEQ ID NO: 3147)MYC-984 19 nt Target #1: 5′-CCAGGACUGUAUGUGGAGC-3′ (SEQ ID NO: 2494)MYC-984 19 nt Target #2: 5′-UCCAGGACUGUAUGUGGAG-3′ (SEQ ID NO: 2821)MYC-984 19 nt Target #3: 5′-AUCCAGGACUGUAUGUGGA-3′ (SEQ ID NO: 3148)MYC-985 19 nt Target #1: 5′-CAGGACUGUAUGUGGAGCG-3′ (SEQ ID NO: 2495)MYC-985 19 nt Target #2: 5′-CCAGGACUGUAUGUGGAGC-3′ (SEQ ID NO: 2822)MYC-985 19 nt Target #3: 5′-UCCAGGACUGUAUGUGGAG-3′ (SEQ ID NO: 3149)MYC-986 19 nt Target #1: 5′-AGGACUGUAUGUGGAGCGG-3′ (SEQ ID NO: 2496)MYC-986 19 nt Target #2: 5′-CAGGACUGUAUGUGGAGCG-3′ (SEQ ID NO: 2823)MYC-986 19 nt Target #3: 5′-CCAGGACUGUAUGUGGAGC-3′ (SEQ ID NO: 3150)MYC-1033 19 nt Target #1: 5′-GAGAAGCUGGCCUCCUACC-3′ (SEQ ID NO: 2497)MYC-1033 19 nt Target #2: 5′-AGAGAAGCUGGCCUCCUAC-3′ (SEQ ID NO: 2824)MYC-1033 19 nt Target #3: 5′-CAGAGAAGCUGGCCUCCUA-3′ (SEQ ID NO: 3151)MYC-1034 19 nt Target #1: 5′-AGAAGCUGGCCUCCUACCA-3′ (SEQ ID NO: 2498)MYC-1034 19 nt Target #2: 5′-GAGAAGCUGGCCUCCUACC-3′ (SEQ ID NO: 2825)MYC-1034 19 nt Target #3: 5′-AGAGAAGCUGGCCUCCUAC-3′ (SEQ ID NO: 3152)MYC-1035 19 nt Target #1: 5′-GAAGCUGGCCUCCUACCAG-3′ (SEQ ID NO: 2499)MYC-1035 19 nt Target #2: 5′-AGAAGCUGGCCUCCUACCA-3′ (SEQ ID NO: 2826)MYC-1035 19 nt Target #3: 5′-GAGAAGCUGGCCUCCUACC-3′ (SEQ ID NO: 3153)MYC-1036 19 nt Target #1: 5′-AAGCUGGCCUCCUACCAGG-3′ (SEQ ID NO: 2500)MYC-1036 19 nt Target #2: 5′-GAAGCUGGCCUCCUACCAG-3′ (SEQ ID NO: 2827)MYC-1036 19 nt Target #3: 5′-AGAAGCUGGCCUCCUACCA-3′ (SEQ ID NO: 3154)MYC-1037 19 nt Target #1: 5′-AGCUGGCCUCCUACCAGGC-3′ (SEQ ID NO: 2501)MYC-1037 19 nt Target #2: 5′-AAGCUGGCCUCCUACCAGG-3′ (SEQ ID NO: 2828)MYC-1037 19 nt Target #3: 5′-GAAGCUGGCCUCCUACCAG-3′ (SEQ ID NO: 3155)MYC-1038 19 nt Target #1: 5′-GCUGGCCUCCUACCAGGCU-3′ (SEQ ID NO: 2502)MYC-1038 19 nt Target #2: 5′-AGCUGGCCUCCUACCAGGC-3′ (SEQ ID NO: 2829)MYC-1038 19 nt Target #3: 5′-AAGCUGGCCUCCUACCAGG-3′ (SEQ ID NO: 3156)MYC-1039 19 nt Target #1: 5′-CUGGCCUCCUACCAGGCUG-3′ (SEQ ID NO: 2503)MYC-1039 19 nt Target #2: 5′-GCUGGCCUCCUACCAGGCU-3′ (SEQ ID NO: 2830)MYC-1039 19 nt Target #3: 5′-AGCUGGCCUCCUACCAGGC-3′ (SEQ ID NO: 3157)MYC-1040 19 nt Target #1: 5′-UGGCCUCCUACCAGGCUGC-3′ (SEQ ID NO: 2504)MYC-1040 19 nt Target #2: 5′-CUGGCCUCCUACCAGGCUG-3′ (SEQ ID NO: 2831)MYC-1040 19 nt Target #3: 5′-GCUGGCCUCCUACCAGGCU-3′ (SEQ ID NO: 3158)MYC-1041 19 nt Target #1: 5′-GGCCUCCUACCAGGCUGCG-3′ (SEQ ID NO: 2505)MYC-1041 19 nt Target #2: 5′-UGGCCUCCUACCAGGCUGC-3′ (SEQ ID NO: 2832)MYC-1041 19 nt Target #3: 5′-CUGGCCUCCUACCAGGCUG-3′ (SEQ ID NO: 3159)MYC-1042 19 nt Target #1: 5′-GCCUCCUACCAGGCUGCGC-3′ (SEQ ID NO: 2506)MYC-1042 19 nt Target #2: 5′-GGCCUCCUACCAGGCUGCG-3′ (SEQ ID NO: 2833)MYC-1042 19 nt Target #3: 5′-UGGCCUCCUACCAGGCUGC-3′ (SEQ ID NO: 3160)MYC-1043 19 nt Target #1: 5′-CCUCCUACCAGGCUGCGCG-3′ (SEQ ID NO: 2507)MYC-1043 19 nt Target #2: 5′-GCCUCCUACCAGGCUGCGC-3′ (SEQ ID NO: 2834)MYC-1043 19 nt Target #3: 5′-GGCCUCCUACCAGGCUGCG-3′ (SEQ ID NO: 3161)MYC-1044 19 nt Target #1: 5′-CUCCUACCAGGCUGCGCGC-3′ (SEQ ID NO: 2508)MYC-1044 19 nt Target #2: 5′-CCUCCUACCAGGCUGCGCG-3′ (SEQ ID NO: 2835)MYC-1044 19 nt Target #3: 5′-GCCUCCUACCAGGCUGCGC-3′ (SEQ ID NO: 3162)MYC-1045 19 nt Target #1: 5′-UCCUACCAGGCUGCGCGCA-3′ (SEQ ID NO: 2509)MYC-1045 19 nt Target #2: 5′-CUCCUACCAGGCUGCGCGC-3′ (SEQ ID NO: 2836)MYC-1045 19 nt Target #3: 5′-CCUCCUACCAGGCUGCGCG-3′ (SEQ ID NO: 3163)MYC-1046 19 nt Target #1: 5′-CCUACCAGGCUGCGCGCAA-3′ (SEQ ID NO: 2510)MYC-1046 19 nt Target #2: 5′-UCCUACCAGGCUGCGCGCA-3′ (SEQ ID NO: 2837)MYC-1046 19 nt Target #3: 5′-CUCCUACCAGGCUGCGCGC-3′ (SEQ ID NO: 3164)MYC-1047 19 nt Target #1: 5′-CUACCAGGCUGCGCGCAAA-3′ (SEQ ID NO: 2511)MYC-1047 19 nt Target #2: 5′-CCUACCAGGCUGCGCGCAA-3′ (SEQ ID NO: 2838)MYC-1047 19 nt Target #3: 5′-UCCUACCAGGCUGCGCGCA-3′ (SEQ ID NO: 3165)MYC-1048 19 nt Target #1: 5′-UACCAGGCUGCGCGCAAAG-3′ (SEQ ID NO: 2512)MYC-1048 19 nt Target #2: 5′-CUACCAGGCUGCGCGCAAA-3′ (SEQ ID NO: 2839)MYC-1048 19 nt Target #3: 5′-CCUACCAGGCUGCGCGCAA-3′ (SEQ ID NO: 3166)MYC-1049 19 nt Target #1: 5′-ACCAGGCUGCGCGCAAAGA-3′ (SEQ ID NO: 2513)MYC-1049 19 nt Target #2: 5′-UACCAGGCUGCGCGCAAAG-3′ (SEQ ID NO: 2840)MYC-1049 19 nt Target #3: 5′-CUACCAGGCUGCGCGCAAA-3′ (SEQ ID NO: 3167)MYC-1050 19 nt Target #1: 5′-CCAGGCUGCGCGCAAAGAC-3′ (SEQ ID NO: 2514)MYC-1050 19 nt Target #2: 5′-ACCAGGCUGCGCGCAAAGA-3′ (SEQ ID NO: 2841)MYC-1050 19 nt Target #3: 5′-UACCAGGCUGCGCGCAAAG-3′ (SEQ ID NO: 3168)MYC-1051 19 nt Target #1: 5′-CAGGCUGCGCGCAAAGACA-3′ (SEQ ID NO: 2515)MYC-1051 19 nt Target #2: 5′-CCAGGCUGCGCGCAAAGAC-3′ (SEQ ID NO: 2842)MYC-1051 19 nt Target #3: 5′-ACCAGGCUGCGCGCAAAGA-3′ (SEQ ID NO: 3169)MYC-1052 19 nt Target #1: 5′-AGGCUGCGCGCAAAGACAG-3′ (SEQ ID NO: 2516)MYC-1052 19 nt Target #2: 5′-CAGGCUGCGCGCAAAGACA-3′ (SEQ ID NO: 2843)MYC-1052 19 nt Target #3: 5′-CCAGGCUGCGCGCAAAGAC-3′ (SEQ ID NO: 3170)MYC-1053 19 nt Target #1: 5′-GGCUGCGCGCAAAGACAGC-3′ (SEQ ID NO: 2517)MYC-1053 19 nt Target #2: 5′-AGGCUGCGCGCAAAGACAG-3′ (SEQ ID NO: 2844)MYC-1053 19 nt Target #3: 5′-CAGGCUGCGCGCAAAGACA-3′ (SEQ ID NO: 3171)MYC-1096 19 nt Target #1: 5′-CACAGCGUCUGCUCCACCU-3′ (SEQ ID NO: 2518)MYC-1096 19 nt Target #2: 5′-CCACAGCGUCUGCUCCACC-3′ (SEQ ID NO: 2845)MYC-1096 19 nt Target #3: 5′-GCCACAGCGUCUGCUCCAC-3′ (SEQ ID NO: 3172)MYC-1097 19 nt Target #1: 5′-ACAGCGUCUGCUCCACCUC-3′ (SEQ ID NO: 2519)MYC-1097 19 nt Target #2: 5′-CACAGCGUCUGCUCCACCU-3′ (SEQ ID NO: 2846)MYC-1097 19 nt Target #3: 5′-CCACAGCGUCUGCUCCACC-3′ (SEQ ID NO: 3173)MYC-1098 19 nt Target #1: 5′-CAGCGUCUGCUCCACCUCC-3′ (SEQ ID NO: 2520)MYC-1098 19 nt Target #2: 5′-ACAGCGUCUGCUCCACCUC-3′ (SEQ ID NO: 2847)MYC-1098 19 nt Target #3: 5′-CACAGCGUCUGCUCCACCU-3′ (SEQ ID NO: 3174)MYC-1099 19 nt Target #1: 5′-AGCGUCUGCUCCACCUCCA-3′ (SEQ ID NO: 2521)MYC-1099 19 nt Target #2: 5′-CAGCGUCUGCUCCACCUCC-3′ (SEQ ID NO: 2848)MYC-1099 19 nt Target #3: 5′-ACAGCGUCUGCUCCACCUC-3′ (SEQ ID NO: 3175)MYC-1100 19 nt Target #1: 5′-GCGUCUGCUCCACCUCCAG-3′ (SEQ ID NO: 2522)MYC-1100 19 nt Target #2: 5′-AGCGUCUGCUCCACCUCCA-3′ (SEQ ID NO: 2849)MYC-1100 19 nt Target #3: 5′-CAGCGUCUGCUCCACCUCC-3′ (SEQ ID NO: 3176)MYC-1101 19 nt Target #1: 5′-CGUCUGCUCCACCUCCAGC-3′ (SEQ ID NO: 2523)MYC-1101 19 nt Target #2: 5′-GCGUCUGCUCCACCUCCAG-3′ (SEQ ID NO: 2850)MYC-1101 19 nt Target #3: 5′-AGCGUCUGCUCCACCUCCA-3′ (SEQ ID NO: 3177)MYC-1189 19 nt Target #1: 5′-CUCAACGACAGCAGCUCGC-3′ (SEQ ID NO: 2524)MYC-1189 19 nt Target #2: 5′-UCUCAACGACAGCAGCUCG-3′ (SEQ ID NO: 2851)MYC-1189 19 nt Target #3: 5′-CUCUCAACGACAGCAGCUC-3′ (SEQ ID NO: 3178)MYC-1190 19 nt Target #1: 5′-UCAACGACAGCAGCUCGCC-3′ (SEQ ID NO: 2525)MYC-1190 19 nt Target #2: 5′-CUCAACGACAGCAGCUCGC-3′ (SEQ ID NO: 2852)MYC-1190 19 nt Target #3: 5′-UCUCAACGACAGCAGCUCG-3′ (SEQ ID NO: 3179)MYC-1191 19 nt Target #1: 5′-CAACGACAGCAGCUCGCCC-3′ (SEQ ID NO: 2526)MYC-1191 19 nt Target #2: 5′-UCAACGACAGCAGCUCGCC-3′ (SEQ ID NO: 2853)MYC-1191 19 nt Target #3: 5′-CUCAACGACAGCAGCUCGC-3′ (SEQ ID NO: 3180)MYC-1192 19 nt Target #1: 5′-AACGACAGCAGCUCGCCCA-3′ (SEQ ID NO: 2527)MYC-1192 19 nt Target #2: 5′-CAACGACAGCAGCUCGCCC-3′ (SEQ ID NO: 2854)MYC-1192 19 nt Target #3: 5′-UCAACGACAGCAGCUCGCC-3′ (SEQ ID NO: 3181)MYC-1193 19 nt Target #1: 5′-ACGACAGCAGCUCGCCCAA-3′ (SEQ ID NO: 2528)MYC-1193 19 nt Target #2: 5′-AACGACAGCAGCUCGCCCA-3′ (SEQ ID NO: 2855)MYC-1193 19 nt Target #3: 5′-CAACGACAGCAGCUCGCCC-3′ (SEQ ID NO: 3182)MYC-1315 19 nt Target #1: 5′-CAUGAGGAGACACCGCCCA-3′ (SEQ ID NO: 2529)MYC-1315 19 nt Target #2: 5′-CCAUGAGGAGACACCGCCC-3′ (SEQ ID NO: 2856)MYC-1315 19 nt Target #3: 5′-UCCAUGAGGAGACACCGCC-3′ (SEQ ID NO: 3183)MYC-1316 19 nt Target #1: 5′-AUGAGGAGACACCGCCCAC-3′ (SEQ ID NO: 2530)MYC-1316 19 nt Target #2: 5′-CAUGAGGAGACACCGCCCA-3′ (SEQ ID NO: 2857)MYC-1316 19 nt Target #3: 5′-CCAUGAGGAGACACCGCCC-3′ (SEQ ID NO: 3184)MYC-1317 19 nt Target #1: 5′-UGAGGAGACACCGCCCACC-3′ (SEQ ID NO: 2531)MYC-1317 19 nt Target #2: 5′-AUGAGGAGACACCGCCCAC-3′ (SEQ ID NO: 2858)MYC-1317 19 nt Target #3: 5′-CAUGAGGAGACACCGCCCA-3′ (SEQ ID NO: 3185)MYC-1318 19 nt Target #1: 5′-GAGGAGACACCGCCCACCA-3′ (SEQ ID NO: 2532)MYC-1318 19 nt Target #2: 5′-UGAGGAGACACCGCCCACC-3′ (SEQ ID NO: 2859)MYC-1318 19 nt Target #3: 5′-AUGAGGAGACACCGCCCAC-3′ (SEQ ID NO: 3186)MYC-1319 19 nt Target #1: 5′-AGGAGACACCGCCCACCAC-3′ (SEQ ID NO: 2533)MYC-1319 19 nt Target #2: 5′-GAGGAGACACCGCCCACCA-3′ (SEQ ID NO: 2860)MYC-1319 19 nt Target #3: 5′-UGAGGAGACACCGCCCACC-3′ (SEQ ID NO: 3187)MYC-1320 19 nt Target #1: 5′-GGAGACACCGCCCACCACC-3′ (SEQ ID NO: 2534)MYC-1320 19 nt Target #2: 5′-AGGAGACACCGCCCACCAC-3′ (SEQ ID NO: 2861)MYC-1320 19 nt Target #3: 5′-GAGGAGACACCGCCCACCA-3′ (SEQ ID NO: 3188)MYC-1321 19 nt Target #1: 5′-GAGACACCGCCCACCACCA-3′ (SEQ ID NO: 2535)MYC-1321 19 nt Target #2: 5′-GGAGACACCGCCCACCACC-3′ (SEQ ID NO: 2862)MYC-1321 19 nt Target #3: 5′-AGGAGACACCGCCCACCAC-3′ (SEQ ID NO: 3189)MYC-1322 19 nt Target #1: 5′-AGACACCGCCCACCACCAG-3′ (SEQ ID NO: 2536)MYC-1322 19 nt Target #2: 5′-GAGACACCGCCCACCACCA-3′ (SEQ ID NO: 2863)MYC-1322 19 nt Target #3: 5′-GGAGACACCGCCCACCACC-3′ (SEQ ID NO: 3190)MYC-1323 19 nt Target #1: 5′-GACACCGCCCACCACCAGC-3′ (SEQ ID NO: 2537)MYC-1323 19 nt Target #2: 5′-AGACACCGCCCACCACCAG-3′ (SEQ ID NO: 2864)MYC-1323 19 nt Target #3: 5′-GAGACACCGCCCACCACCA-3′ (SEQ ID NO: 3191)MYC-1324 19 nt Target #1: 5′-ACACCGCCCACCACCAGCA-3′ (SEQ ID NO: 2538)MYC-1324 19 nt Target #2: 5′-GACACCGCCCACCACCAGC-3′ (SEQ ID NO: 2865)MYC-1324 19 nt Target #3: 5′-AGACACCGCCCACCACCAG-3′ (SEQ ID NO: 3192)MYC-1325 19 nt Target #1: 5′-CACCGCCCACCACCAGCAG-3′ (SEQ ID NO: 2539)MYC-1325 19 nt Target #2: 5′-ACACCGCCCACCACCAGCA-3′ (SEQ ID NO: 2866)MYC-1325 19 nt Target #3: 5′-GACACCGCCCACCACCAGC-3′ (SEQ ID NO: 3193)MYC-1326 19 nt Target #1: 5′-ACCGCCCACCACCAGCAGC-3′ (SEQ ID NO: 2540)MYC-1326 19 nt Target #2: 5′-CACCGCCCACCACCAGCAG-3′ (SEQ ID NO: 2867)MYC-1326 19 nt Target #3: 5′-ACACCGCCCACCACCAGCA-3′ (SEQ ID NO: 3194)MYC-1327 19 nt Target #1: 5′-CCGCCCACCACCAGCAGCG-3′ (SEQ ID NO: 2541)MYC-1327 19 nt Target #2: 5′-ACCGCCCACCACCAGCAGC-3′ (SEQ ID NO: 2868)MYC-1327 19 nt Target #3: 5′-CACCGCCCACCACCAGCAG-3′ (SEQ ID NO: 3195)MYC-1328 19 nt Target #1: 5′-CGCCCACCACCAGCAGCGA-3′ (SEQ ID NO: 2542)MYC-1328 19 nt Target #2: 5′-CCGCCCACCACCAGCAGCG-3′ (SEQ ID NO: 2869)MYC-1328 19 nt Target #3: 5′-ACCGCCCACCACCAGCAGC-3′ (SEQ ID NO: 3196)MYC-1329 19 nt Target #1: 5′-GCCCACCACCAGCAGCGAC-3′ (SEQ ID NO: 2543)MYC-1329 19 nt Target #2: 5′-CGCCCACCACCAGCAGCGA-3′ (SEQ ID NO: 2870)MYC-1329 19 nt Target #3: 5′-CCGCCCACCACCAGCAGCG-3′ (SEQ ID NO: 3197)MYC-1330 19 nt Target #1: 5′-CCCACCACCAGCAGCGACU-3′ (SEQ ID NO: 2544)MYC-1330 19 nt Target #2: 5′-GCCCACCACCAGCAGCGAC-3′ (SEQ ID NO: 2871)MYC-1330 19 nt Target #3: 5′-CGCCCACCACCAGCAGCGA-3′ (SEQ ID NO: 3198)MYC-1331 19 nt Target #1: 5′-CCACCACCAGCAGCGACUC-3′ (SEQ ID NO: 2545)MYC-1331 19 nt Target #2: 5′-CCCACCACCAGCAGCGACU-3′ (SEQ ID NO: 2872)MYC-1331 19 nt Target #3: 5′-GCCCACCACCAGCAGCGAC-3′ (SEQ ID NO: 3199)MYC-1332 19 nt Target #1: 5′-CACCACCAGCAGCGACUCU-3′ (SEQ ID NO: 2546)MYC-1332 19 nt Target #2: 5′-CCACCACCAGCAGCGACUC-3′ (SEQ ID NO: 2873)MYC-1332 19 nt Target #3: 5′-CCCACCACCAGCAGCGACU-3′ (SEQ ID NO: 3200)MYC-1333 19 nt Target #1: 5′-ACCACCAGCAGCGACUCUG-3′ (SEQ ID NO: 2547)MYC-1333 19 nt Target #2: 5′-CACCACCAGCAGCGACUCU-3′ (SEQ ID NO: 2874)MYC-1333 19 nt Target #3: 5′-CCACCACCAGCAGCGACUC-3′ (SEQ ID NO: 3201)MYC-1334 19 nt Target #1: 5′-CCACCAGCAGCGACUCUGA-3′ (SEQ ID NO: 2548)MYC-1334 19 nt Target #2: 5′-ACCACCAGCAGCGACUCUG-3′ (SEQ ID NO: 2875)MYC-1334 19 nt Target #3: 5′-CACCACCAGCAGCGACUCU-3′ (SEQ ID NO: 3202)MYC-1360 19 nt Target #1: 5′-CAAGAAGAUGAGGAAGAAA-3′ (SEQ ID NO: 2549)MYC-1360 19 nt Target #2: 5′-ACAAGAAGAUGAGGAAGAA-3′ (SEQ ID NO: 2876)MYC-1360 19 nt Target #3: 5′-AACAAGAAGAUGAGGAAGA-3′ (SEQ ID NO: 3203)MYC-1361 19 nt Target #1: 5′-AAGAAGAUGAGGAAGAAAU-3′ (SEQ ID NO: 2550)MYC-1361 19 nt Target #2: 5′-CAAGAAGAUGAGGAAGAAA-3′ (SEQ ID NO: 2877)MYC-1361 19 nt Target #3: 5′-ACAAGAAGAUGAGGAAGAA-3′ (SEQ ID NO: 3204)MYC-1448 19 nt Target #1: 5′-GAGGCCACAGCAAACCUCC-3′ (SEQ ID NO: 2551)MYC-1448 19 nt Target #2: 5′-GGAGGCCACAGCAAACCUC-3′ (SEQ ID NO: 2878)MYC-1448 19 nt Target #3: 5′-UGGAGGCCACAGCAAACCU-3′ (SEQ ID NO: 3205)MYC-1468 19 nt Target #1: 5′-CACAGCCCACUGGUCCUCA-3′ (SEQ ID NO: 2552)MYC-1468 19 nt Target #2: 5′-UCACAGCCCACUGGUCCUC-3′ (SEQ ID NO: 2879)MYC-1468 19 nt Target #3: 5′-CUCACAGCCCACUGGUCCU-3′ (SEQ ID NO: 3206)MYC-1469 19 nt Target #1: 5′-ACAGCCCACUGGUCCUCAA-3′ (SEQ ID NO: 2553)MYC-1469 19 nt Target #2: 5′-CACAGCCCACUGGUCCUCA-3′ (SEQ ID NO: 2880)MYC-1469 19 nt Target #3: 5′-UCACAGCCCACUGGUCCUC-3′ (SEQ ID NO: 3207)MYC-1470 19 nt Target #1: 5′-CAGCCCACUGGUCCUCAAG-3′ (SEQ ID NO: 2554)MYC-1470 19 nt Target #2: 5′-ACAGCCCACUGGUCCUCAA-3′ (SEQ ID NO: 2881)MYC-1470 19 nt Target #3: 5′-CACAGCCCACUGGUCCUCA-3′ (SEQ ID NO: 3208)MYC-1471 19 nt Target #1: 5′-AGCCCACUGGUCCUCAAGA-3′ (SEQ ID NO: 2555)MYC-1471 19 nt Target #2: 5′-CAGCCCACUGGUCCUCAAG-3′ (SEQ ID NO: 2882)MYC-1471 19 nt Target #3: 5′-ACAGCCCACUGGUCCUCAA-3′ (SEQ ID NO: 3209)MYC-1472 19 nt Target #1: 5′-GCCCACUGGUCCUCAAGAG-3′ (SEQ ID NO: 2556)MYC-1472 19 nt Target #2: 5′-AGCCCACUGGUCCUCAAGA-3′ (SEQ ID NO: 2883)MYC-1472 19 nt Target #3: 5′-CAGCCCACUGGUCCUCAAG-3′ (SEQ ID NO: 3210)MYC-1473 19 nt Target #1: 5′-CCCACUGGUCCUCAAGAGG-3′ (SEQ ID NO: 2557)MYC-1473 19 nt Target #2: 5′-GCCCACUGGUCCUCAAGAG-3′ (SEQ ID NO: 2884)MYC-1473 19 nt Target #3: 5′-AGCCCACUGGUCCUCAAGA-3′ (SEQ ID NO: 3211)MYC-1474 19 nt Target #1: 5′-CCACUGGUCCUCAAGAGGU-3′ (SEQ ID NO: 2558)MYC-1474 19 nt Target #2: 5′-CCCACUGGUCCUCAAGAGG-3′ (SEQ ID NO: 2885)MYC-1474 19 nt Target #3: 5′-GCCCACUGGUCCUCAAGAG-3′ (SEQ ID NO: 3212)MYC-1475 19 nt Target #1: 5′-CACUGGUCCUCAAGAGGUG-3′ (SEQ ID NO: 2559)MYC-1475 19 nt Target #2: 5′-CCACUGGUCCUCAAGAGGU-3′ (SEQ ID NO: 2886)MYC-1475 19 nt Target #3: 5′-CCCACUGGUCCUCAAGAGG-3′ (SEQ ID NO: 3213)MYC-1476 19 nt Target #1: 5′-ACUGGUCCUCAAGAGGUGC-3′ (SEQ ID NO: 2560)MYC-1476 19 nt Target #2: 5′-CACUGGUCCUCAAGAGGUG-3′ (SEQ ID NO: 2887)MYC-1476 19 nt Target #3: 5′-CCACUGGUCCUCAAGAGGU-3′ (SEQ ID NO: 3214)MYC-1477 19 nt Target #1: 5′-CUGGUCCUCAAGAGGUGCC-3′ (SEQ ID NO: 2561)MYC-1477 19 nt Target #2: 5′-ACUGGUCCUCAAGAGGUGC-3′ (SEQ ID NO: 2888)MYC-1477 19 nt Target #3: 5′-CACUGGUCCUCAAGAGGUG-3′ (SEQ ID NO: 3215)MYC-1478 19 nt Target #1: 5′-UGGUCCUCAAGAGGUGCCA-3′ (SEQ ID NO: 2562)MYC-1478 19 nt Target #2: 5′-CUGGUCCUCAAGAGGUGCC-3′ (SEQ ID NO: 2889)MYC-1478 19 nt Target #3: 5′-ACUGGUCCUCAAGAGGUGC-3′ (SEQ ID NO: 3216)MYC-1479 19 nt Target #1: 5′-GGUCCUCAAGAGGUGCCAC-3′ (SEQ ID NO: 2563)MYC-1479 19 nt Target #2: 5′-UGGUCCUCAAGAGGUGCCA-3′ (SEQ ID NO: 2890)MYC-1479 19 nt Target #3: 5′-CUGGUCCUCAAGAGGUGCC-3′ (SEQ ID NO: 3217)MYC-1480 19 nt Target #1: 5′-GUCCUCAAGAGGUGCCACG-3′ (SEQ ID NO: 2564)MYC-1480 19 nt Target #2: 5′-GGUCCUCAAGAGGUGCCAC-3′ (SEQ ID NO: 2891)MYC-1480 19 nt Target #3: 5′-UGGUCCUCAAGAGGUGCCA-3′ (SEQ ID NO: 3218)MYC-1481 19 nt Target #1: 5′-UCCUCAAGAGGUGCCACGU-3′ (SEQ ID NO: 2565)MYC-1481 19 nt Target #2: 5′-GUCCUCAAGAGGUGCCACG-3′ (SEQ ID NO: 2892)MYC-1481 19 nt Target #3: 5′-GGUCCUCAAGAGGUGCCAC-3′ (SEQ ID NO: 3219)MYC-1482 19 nt Target #1: 5′-CCUCAAGAGGUGCCACGUC-3′ (SEQ ID NO: 2566)MYC-1482 19 nt Target #2: 5′-UCCUCAAGAGGUGCCACGU-3′ (SEQ ID NO: 2893)MYC-1482 19 nt Target #3: 5′-GUCCUCAAGAGGUGCCACG-3′ (SEQ ID NO: 3220)MYC-1483 19 nt Target #1: 5′-CUCAAGAGGUGCCACGUCU-3′ (SEQ ID NO: 2567)MYC-1483 19 nt Target #2: 5′-CCUCAAGAGGUGCCACGUC-3′ (SEQ ID NO: 2894)MYC-1483 19 nt Target #3: 5′-UCCUCAAGAGGUGCCACGU-3′ (SEQ ID NO: 3221)MYC-1711 19 nt Target #1: 5′-AGCUUUUUUGCCCUGCGUG-3′ (SEQ ID NO: 2568)MYC-1711 19 nt Target #2: 5′-GAGCUUUUUUGCCCUGCGU-3′ (SEQ ID NO: 2895)MYC-1711 19 nt Target #3: 5′-GGAGCUUUUUUGCCCUGCG-3′ (SEQ ID NO: 3222)MYC-1712 19 nt Target #1: 5′-GCUUUUUUGCCCUGCGUGA-3′ (SEQ ID NO: 2569)MYC-1712 19 nt Target #2: 5′-AGCUUUUUUGCCCUGCGUG-3′ (SEQ ID NO: 2896)MYC-1712 19 nt Target #3: 5′-GAGCUUUUUUGCCCUGCGU-3′ (SEQ ID NO: 3223)MYC-1713 19 nt Target #1: 5′-CUUUUUUGCCCUGCGUGAC-3′ (SEQ ID NO: 2570)MYC-1713 19 nt Target #2: 5′-GCUUUUUUGCCCUGCGUGA-3′ (SEQ ID NO: 2897)MYC-1713 19 nt Target #3: 5′-AGCUUUUUUGCCCUGCGUG-3′ (SEQ ID NO: 3224)MYC-1714 19 nt Target #1: 5′-UUUUUUGCCCUGCGUGACC-3′ (SEQ ID NO: 2571)MYC-1714 19 nt Target #2: 5′-CUUUUUUGCCCUGCGUGAC-3′ (SEQ ID NO: 2898)MYC-1714 19 nt Target #3: 5′-GCUUUUUUGCCCUGCGUGA-3′ (SEQ ID NO: 3225)MYC-1715 19 nt Target #1: 5′-UUUUUGCCCUGCGUGACCA-3′ (SEQ ID NO: 2572)MYC-1715 19 nt Target #2: 5′-UUUUUUGCCCUGCGUGACC-3′ (SEQ ID NO: 2899)MYC-1715 19 nt Target #3: 5′-CUUUUUUGCCCUGCGUGAC-3′ (SEQ ID NO: 3226)MYC-1716 19 nt Target #1: 5′-UUUUGCCCUGCGUGACCAG-3′ (SEQ ID NO: 2573)MYC-1716 19 nt Target #2: 5′-UUUUUGCCCUGCGUGACCA-3′ (SEQ ID NO: 2900)MYC-1716 19 nt Target #3: 5′-UUUUUUGCCCUGCGUGACC-3′ (SEQ ID NO: 3227)MYC-1717 19 nt Target #1: 5′-UUUGCCCUGCGUGACCAGA-3′ (SEQ ID NO: 2574)MYC-1717 19 nt Target #2: 5′-UUUUGCCCUGCGUGACCAG-3′ (SEQ ID NO: 2901)MYC-1717 19 nt Target #3: 5′-UUUUUGCCCUGCGUGACCA-3′ (SEQ ID NO: 3228)MYC-1718 19 nt Target #1: 5′-UUGCCCUGCGUGACCAGAU-3′ (SEQ ID NO: 2575)MYC-1718 19 nt Target #2: 5′-UUUGCCCUGCGUGACCAGA-3′ (SEQ ID NO: 2902)MYC-1718 19 nt Target #3: 5′-UUUUGCCCUGCGUGACCAG-3′ (SEQ ID NO: 3229)MYC-1719 19 nt Target #1: 5′-UGCCCUGCGUGACCAGAUC-3′ (SEQ ID NO: 2576)MYC-1719 19 nt Target #2: 5′-UUGCCCUGCGUGACCAGAU-3′ (SEQ ID NO: 2903)MYC-1719 19 nt Target #3: 5′-UUUGCCCUGCGUGACCAGA-3′ (SEQ ID NO: 3230)MYC-1720 19 nt Target #1: 5′-GCCCUGCGUGACCAGAUCC-3′ (SEQ ID NO: 2577)MYC-1720 19 nt Target #2: 5′-UGCCCUGCGUGACCAGAUC-3′ (SEQ ID NO: 2904)MYC-1720 19 nt Target #3: 5′-UUGCCCUGCGUGACCAGAU-3′ (SEQ ID NO: 3231)MYC-1721 19 nt Target #1: 5′-CCCUGCGUGACCAGAUCCC-3′ (SEQ ID NO: 2578)MYC-1721 19 nt Target #2: 5′-GCCCUGCGUGACCAGAUCC-3′ (SEQ ID NO: 2905)MYC-1721 19 nt Target #3: 5′-UGCCCUGCGUGACCAGAUC-3′ (SEQ ID NO: 3232)MYC-1856 19 nt Target #1: 5′-GGAAACGACGAGAACAGUU-3′ (SEQ ID NO: 2579)MYC-1856 19 nt Target #2: 5′-CGGAAACGACGAGAACAGU-3′ (SEQ ID NO: 2906)MYC-1856 19 nt Target #3: 5′-GCGGAAACGACGAGAACAG-3′ (SEQ ID NO: 3233)MYC-1857 19 nt Target #1: 5′-GAAACGACGAGAACAGUUG-3′ (SEQ ID NO: 2580)MYC-1857 19 nt Target #2: 5′-GGAAACGACGAGAACAGUU-3′ (SEQ ID NO: 2907)MYC-1857 19 nt Target #3: 5′-CGGAAACGACGAGAACAGU-3′ (SEQ ID NO: 3234)MYC-2115 19 nt Target #1: 5′-UUUAACAGAUUUGUAUUUA-3′ (SEQ ID NO: 2581)MYC-2115 19 nt Target #2: 5′-CUUUAACAGAUUUGUAUUU-3′ (SEQ ID NO: 2908)MYC-2115 19 nt Target #3: 5′-UCUUUAACAGAUUUGUAUU-3′ (SEQ ID NO: 3235)MYC-2116 19 nt Target #1: 5′-UUAACAGAUUUGUAUUUAA-3′ (SEQ ID NO: 2582)MYC-2116 19 nt Target #2: 5′-UUUAACAGAUUUGUAUUUA-3′ (SEQ ID NO: 2909)MYC-2116 19 nt Target #3: 5′-CUUUAACAGAUUUGUAUUU-3′ (SEQ ID NO: 3236)MYC-2193 19 nt Target #1: 5′-AAAUGUAAAUAACUUUAAU-3′ (SEQ ID NO: 2583)MYC-2193 19 nt Target #2: 5′-UAAAUGUAAAUAACUUUAA-3′ (SEQ ID NO: 2910)MYC-2193 19 nt Target #3: 5′-UUAAAUGUAAAUAACUUUA-3′ (SEQ ID NO: 3237)MYC-2194 19 nt Target #1: 5′-AAUGUAAAUAACUUUAAUA-3′ (SEQ ID NO: 2584)MYC-2194 19 nt Target #2: 5′-AAAUGUAAAUAACUUUAAU-3′ (SEQ ID NO: 2911)MYC-2194 19 nt Target #3: 5′-UAAAUGUAAAUAACUUUAA-3′ (SEQ ID NO: 3238)MYC-2195 19 nt Target #1: 5′-AUGUAAAUAACUUUAAUAA-3′ (SEQ ID NO: 2585)MYC-2195 19 nt Target #2: 5′-AAUGUAAAUAACUUUAAUA-3′ (SEQ ID NO: 2912)MYC-2195 19 nt Target #3: 5′-AAAUGUAAAUAACUUUAAU-3′ (SEQ ID NO: 3239)MYC-2196 19 nt Target #1: 5′-UGUAAAUAACUUUAAUAAA-3′ (SEQ ID NO: 2586)MYC-2196 19 nt Target #2: 5′-AUGUAAAUAACUUUAAUAA-3′ (SEQ ID NO: 2913)MYC-2196 19 nt Target #3: 5′-AAUGUAAAUAACUUUAAUA-3′ (SEQ ID NO: 3240)MYC-2197 19 nt Target #1: 5′-GUAAAUAACUUUAAUAAAA-3′ (SEQ ID NO: 2587)MYC-2197 19 nt Target #2: 5′-UGUAAAUAACUUUAAUAAA-3′ (SEQ ID NO: 2914)MYC-2197 19 nt Target #3: 5′-AUGUAAAUAACUUUAAUAA-3′ (SEQ ID NO: 3241)MYC-2198 19 nt Target #1: 5′-UAAAUAACUUUAAUAAAAC-3′ (SEQ ID NO: 2588)MYC-2198 19 nt Target #2: 5′-GUAAAUAACUUUAAUAAAA-3′ (SEQ ID NO: 2915)MYC-2198 19 nt Target #3: 5′-UGUAAAUAACUUUAAUAAA-3′ (SEQ ID NO: 3242)MYC-2199 19 nt Target #1: 5′-AAAUAACUUUAAUAAAACG-3′ (SEQ ID NO: 2589)MYC-2199 19 nt Target #2: 5′-UAAAUAACUUUAAUAAAAC-3′ (SEQ ID NO: 2916)MYC-2199 19 nt Target #3: 5′-GUAAAUAACUUUAAUAAAA-3′ (SEQ ID NO: 3243)MYC-2200 19 nt Target #1: 5′-AAUAACUUUAAUAAAACGU-3′ (SEQ ID NO: 2590)MYC-2200 19 nt Target #2: 5′-AAAUAACUUUAAUAAAACG-3′ (SEQ ID NO: 2917)MYC-2200 19 nt Target #3: 5′-UAAAUAACUUUAAUAAAAC-3′ (SEQ ID NO: 3244)MYC-2201 19 nt Target #1: 5′-AUAACUUUAAUAAAACGUU-3′ (SEQ ID NO: 2591)MYC-2201 19 nt Target #2: 5′-AAUAACUUUAAUAAAACGU-3′ (SEQ ID NO: 2918)MYC-2201 19 nt Target #3: 5′-AAAUAACUUUAAUAAAACG-3′ (SEQ ID NO: 3245)MYC-2202 19 nt Target #1: 5′-UAACUUUAAUAAAACGUUU-3′ (SEQ ID NO: 2592)MYC-2202 19 nt Target #2: 5′-AUAACUUUAAUAAAACGUU-3′ (SEQ ID NO: 2919)MYC-2202 19 nt Target #3: 5′-AAUAACUUUAAUAAAACGU-3′ (SEQ ID NO: 3246)MYC-2203 19 nt Target #1: 5′-AACUUUAAUAAAACGUUUA-3′ (SEQ ID NO: 2593)MYC-2203 19 nt Target #2: 5′-UAACUUUAAUAAAACGUUU-3′ (SEQ ID NO: 2920)MYC-2203 19 nt Target #3: 5′-AUAACUUUAAUAAAACGUU-3′ (SEQ ID NO: 3247)MYC-2204 19 nt Target #1: 5′-ACUUUAAUAAAACGUUUAU-3′ (SEQ ID NO: 2594)MYC-2204 19 nt Target #2: 5′-AACUUUAAUAAAACGUUUA-3′ (SEQ ID NO: 2921)MYC-2204 19 nt Target #3: 5′-UAACUUUAAUAAAACGUUU-3′ (SEQ ID NO: 3248)MYC-2205 19 nt Target #1: 5′-CUUUAAUAAAACGUUUAUA-3′ (SEQ ID NO: 2595)MYC-2205 19 nt Target #2: 5′-ACUUUAAUAAAACGUUUAU-3′ (SEQ ID NO: 2922)MYC-2205 19 nt Target #3: 5′-AACUUUAAUAAAACGUUUA-3′ (SEQ ID NO: 3249)MYC-2313 19 nt Target #1: 5′-UUUUUAAAGUUGAUUUUUU-3′ (SEQ ID NO: 2596)MYC-2313 19 nt Target #2: 5′-CUUUUUAAAGUUGAUUUUU-3′ (SEQ ID NO: 2923)MYC-2313 19 nt Target #3: 5′-GCUUUUUAAAGUUGAUUUU-3′ (SEQ ID NO: 3250)MYC-2314 19 nt Target #1: 5′-UUUUAAAGUUGAUUUUUUU-3′ (SEQ ID NO: 2597)MYC-2314 19 nt Target #2: 5′-UUUUUAAAGUUGAUUUUUU-3′ (SEQ ID NO: 2924)MYC-2314 19 nt Target #3: 5′-CUUUUUAAAGUUGAUUUUU-3′ (SEQ ID NO: 3251)MYC-2315 19 nt Target #1: 5′-UUUAAAGUUGAUUUUUUUC-3′ (SEQ ID NO: 2598)MYC-2315 19 nt Target #2: 5′-UUUUAAAGUUGAUUUUUUU-3′ (SEQ ID NO: 2925)MYC-2315 19 nt Target #3: 5′-UUUUUAAAGUUGAUUUUUU-3′ (SEQ ID NO: 3252)MYC-2316 19 nt Target #1: 5′-UUAAAGUUGAUUUUUUUCU-3′ (SEQ ID NO: 2599)MYC-2316 19 nt Target #2: 5′-UUUAAAGUUGAUUUUUUUC-3′ (SEQ ID NO: 2926)MYC-2316 19 nt Target #3: 5′-UUUUAAAGUUGAUUUUUUU-3′ (SEQ ID NO: 3253)MYC-2317 19 nt Target #1: 5′-UAAAGUUGAUUUUUUUCUA-3′ (SEQ ID NO: 2600)MYC-2317 19 nt Target #2: 5′-UUAAAGUUGAUUUUUUUCU-3′ (SEQ ID NO: 2927)MYC-2317 19 nt Target #3: 5′-UUUAAAGUUGAUUUUUUUC-3′ (SEQ ID NO: 3254)MYC-2318 19 nt Target #1: 5′-AAAGUUGAUUUUUUUCUAU-3′ (SEQ ID NO: 2601)MYC-2318 19 nt Target #2: 5′-UAAAGUUGAUUUUUUUCUA-3′ (SEQ ID NO: 2928)MYC-2318 19 nt Target #3: 5′-UUAAAGUUGAUUUUUUUCU-3′ (SEQ ID NO: 3255)MYC-2319 19 nt Target #1: 5′-AAGUUGAUUUUUUUCUAUU-3′ (SEQ ID NO: 2602)MYC-2319 19 nt Target #2: 5′-AAAGUUGAUUUUUUUCUAU-3′ (SEQ ID NO: 2929)MYC-2319 19 nt Target #3: 5′-UAAAGUUGAUUUUUUUCUA-3′ (SEQ ID NO: 3256)MYC-2320 19 nt Target #1: 5′-AGUUGAUUUUUUUCUAUUG-3′ (SEQ ID NO: 2603)MYC-2320 19 nt Target #2: 5′-AAGUUGAUUUUUUUCUAUU-3′ (SEQ ID NO: 2930)MYC-2320 19 nt Target #3: 5′-AAAGUUGAUUUUUUUCUAU-3′ (SEQ ID NO: 3257)MYC-2321 19 nt Target #1: 5′-GUUGAUUUUUUUCUAUUGU-3′ (SEQ ID NO: 2604)MYC-2321 19 nt Target #2: 5′-AGUUGAUUUUUUUCUAUUG-3′ (SEQ ID NO: 2931)MYC-2321 19 nt Target #3: 5′-AAGUUGAUUUUUUUCUAUU-3′ (SEQ ID NO: 3258)MYC-2322 19 nt Target #1: 5′-UUGAUUUUUUUCUAUUGUU-3′ (SEQ ID NO: 2605)MYC-2322 19 nt Target #2: 5′-GUUGAUUUUUUUCUAUUGU-3′ (SEQ ID NO: 2932)MYC-2322 19 nt Target #3: 5′-AGUUGAUUUUUUUCUAUUG-3′ (SEQ ID NO: 3259)MYC-2323 19 nt Target #1: 5′-UGAUUUUUUUCUAUUGUUU-3′ (SEQ ID NO: 2606)MYC-2323 19 nt Target #2: 5′-UUGAUUUUUUUCUAUUGUU-3′ (SEQ ID NO: 2933)MYC-2323 19 nt Target #3: 5′-GUUGAUUUUUUUCUAUUGU-3′ (SEQ ID NO: 3260)MYC-2324 19 nt Target #1: 5′-GAUUUUUUUCUAUUGUUUU-3′ (SEQ ID NO: 2607)MYC-2324 19 nt Target #2: 5′-UGAUUUUUUUCUAUUGUUU-3′ (SEQ ID NO: 2934)MYC-2324 19 nt Target #3: 5′-UUGAUUUUUUUCUAUUGUU-3′ (SEQ ID NO: 3261)MYC-2325 19 nt Target #1: 5′-AUUUUUUUCUAUUGUUUUU-3′ (SEQ ID NO: 2608)MYC-2325 19 nt Target #2: 5′-GAUUUUUUUCUAUUGUUUU-3′ (SEQ ID NO: 2935)MYC-2325 19 nt Target #3: 5′-UGAUUUUUUUCUAUUGUUU-3′ (SEQ ID NO: 3262)MYC-2326 19 nt Target #1: 5′-UUUUUUUCUAUUGUUUUUA-3′ (SEQ ID NO: 2609)MYC-2326 19 nt Target #2: 5′-AUUUUUUUCUAUUGUUUUU-3′ (SEQ ID NO: 2936)MYC-2326 19 nt Target #3: 5′-GAUUUUUUUCUAUUGUUUU-3′ (SEQ ID NO: 3263)MYC-2327 19 nt Target #1: 5′-UUUUUUCUAUUGUUUUUAG-3′ (SEQ ID NO: 2610)MYC-2327 19 nt Target #2: 5′-UUUUUUUCUAUUGUUUUUA-3′ (SEQ ID NO: 2937)MYC-2327 19 nt Target #3: 5′-AUUUUUUUCUAUUGUUUUU-3′ (SEQ ID NO: 3264)MYC-2328 19 nt Target #1: 5′-UUUUUCUAUUGUUUUUAGA-3′ (SEQ ID NO: 2611)MYC-2328 19 nt Target #2: 5′-UUUUUUCUAUUGUUUUUAG-3′ (SEQ ID NO: 2938)MYC-2328 19 nt Target #3: 5′-UUUUUUUCUAUUGUUUUUA-3′ (SEQ ID NO: 3265)MYC-2329 19 nt Target #1: 5′-UUUUCUAUUGUUUUUAGAA-3′ (SEQ ID NO: 2612)MYC-2329 19 nt Target #2: 5′-UUUUUCUAUUGUUUUUAGA-3′ (SEQ ID NO: 2939)MYC-2329 19 nt Target #3: 5′-UUUUUUCUAUUGUUUUUAG-3′ (SEQ ID NO: 3266)MYC-2330 19 nt Target #1: 5′-UUUCUAUUGUUUUUAGAAA-3′ (SEQ ID NO: 2613)MYC-2330 19 nt Target #2: 5′-UUUUCUAUUGUUUUUAGAA-3′ (SEQ ID NO: 2940)MYC-2330 19 nt Target #3: 5′-UUUUUCUAUUGUUUUUAGA-3′ (SEQ ID NO: 3267)MYC-2331 19 nt Target #1: 5′-UUCUAUUGUUUUUAGAAAA-3′ (SEQ ID NO: 2614)MYC-2331 19 nt Target #2: 5′-UUUCUAUUGUUUUUAGAAA-3′ (SEQ ID NO: 2941)MYC-2331 19 nt Target #3: 5′-UUUUCUAUUGUUUUUAGAA-3′ (SEQ ID NO: 3268)MYC-2332 19 nt Target #1: 5′-UCUAUUGUUUUUAGAAAAA-3′ (SEQ ID NO: 2615)MYC-2332 19 nt Target #2: 5′-UUCUAUUGUUUUUAGAAAA-3′ (SEQ ID NO: 2942)MYC-2332 19 nt Target #3: 5′-UUUCUAUUGUUUUUAGAAA-3′ (SEQ ID NO: 3269)MYC-2333 19 nt Target #1: 5′-CUAUUGUUUUUAGAAAAAA-3′ (SEQ ID NO: 2616)MYC-2333 19 nt Target #2: 5′-UCUAUUGUUUUUAGAAAAA-3′ (SEQ ID NO: 2943)MYC-2333 19 nt Target #3: 5′-UUCUAUUGUUUUUAGAAAA-3′ (SEQ ID NO: 3270)

Within Tables 2-4 and 6-7 above, underlined residues indicate2′-O-methyl residues, UPPER CASE indicates ribonucleotides, and lowercase denotes deoxyribonucleotides. The DsiRNA agents of Tables 2-4 aboveare 25/27mer agents possessing a blunt end. The structures and/ormodification patterning of the agents of Tables 2-4 above can be readilyadapted to the above generic sequence structures, e.g., the 3′ overhangof the second strand can be extended or contracted, 2′-O-methylation ofthe second strand can be expanded towards the 5′ end of the secondstrand, optionally at alternating sites, etc. Such further modificationsare optional, as 25/27mer DsiRNAs with such modifications can also bereadily designed from the above DsiRNA agents and are also expected tobe functional inhibitors of MYC expression. Similarly, the 27mer“blunt/fray” and “blunt/blunt” DsiRNA structures and/or modificationpatterns of the agents of Tables 6-7 above can also be readily adaptedto the above generic sequence structures, e.g., for application ofmodification patterning of the antisense strand to such structuresand/or adaptation of such sequences to the above generic structures.

In certain embodiments, 27mer DsiRNAs possessing independent strandlengths each of 27 nucleotides are designed and synthesized fortargeting of the same sites within the MYC transcript as the asymmetric“25/27” structures shown in Tables 2-4 herein. Exemplary “27/27” DsiRNAsare optionally designed with a “blunt/fray” structure as shown for theDsiRNAs of Table 6 above, or with a “blunt/blunt” structure as shown forthe DsiRNAs of Table 7 above.

In certain embodiments, the dsRNA agents of the invention require, e.g.,at least 19, at least 20, at least 21, at least 22, at least 23, atleast 24, at least 25 or at least 26 residues of the first strand to becomplementary to corresponding residues of the second strand. In certainrelated embodiments, these first strand residues complementary tocorresponding residues of the second strand are optionally consecutiveresidues.

By definition, “sufficiently complementary” (contrasted with, e.g.,“100% complementary”) allows for one or more mismatches to exist betweena dsRNA of the invention and the target RNA or cDNA sequence (e.g., MYCmRNA), provided that the dsRNA possesses complementarity sufficient totrigger the destruction of the target RNA by the RNAi machinery (e.g.,the RISC complex) or process. In certain embodiments, a “sufficientlycomplementary” dsRNA of the invention can harbor one, two, three or evenfour or more mismatches between the dsRNA sequence and the target RNA orcDNA sequence (e.g., in certain such embodiments, the antisense strandof the dsRNA harbors one, two, three, four, five or even six or moremismatches when aligned with the target RNA or cDNA sequence).Additional consideration of the preferred location of such mismatcheswithin certain dsRNAs of the instant invention is considered in greaterdetail below.

As used herein “DsiRNAmm” refers to a DisRNA having a “mismatch tolerantregion” containing one, two, three or four mismatched base pairs of theduplex formed by the sense and antisense strands of the DsiRNA, wheresuch mismatches are positioned within the DsiRNA at a location(s) lyingbetween (and thus not including) the two terminal base pairs of eitherend of the DsiRNA. The mismatched base pairs are located within a“mismatch-tolerant region” which is defined herein with respect to thelocation of the projected Ago2 cut site of the corresponding targetnucleic acid. The mismatch tolerant region is located “upstream of” theprojected Ago2 cut site of the target strand. “Upstream” in this contextwill be understood as the 5′-most portion of the DsiRNAmm duplex, where5′ refers to the orientation of the sense strand of the DsiRNA duplex.Therefore, the mismatch tolerant region is upstream of the base on thesense (passenger) strand that corresponds to the projected Ago2 cut siteof the target nucleic acid (see FIG. 1); alternatively, when referringto the antisense (guide) strand of the DsiRNAmm, the mismatch tolerantregion can also be described as positioned downstream of the base thatis complementary to the projected Ago2 cut site of the target nucleicacid, that is, the 3′-most portion of the antisense strand of theDsiRNAmm (where position 1 of the antisense strand is the 5′ terminalnucleotide of the antisense strand, see FIG. 1).

In one embodiment, for example with numbering as depicted in FIG. 1, themismatch tolerant region is positioned between and including base pairs3-9 when numbered from the nucleotide starting at the 5′ end of thesense strand of the duplex. Therefore, a DsiRNAmm of the inventionpossesses a single mismatched base pair at any one of positions 3, 4, 5,6, 7, 8 or 9 of the sense strand of a right-hand extended DsiRNA (whereposition 1 is the 5′ terminal nucleotide of the sense strand andposition 9 is the nucleotide residue of the sense strand that isimmediately 5′ of the projected Ago2 cut site of the target MYC RNAsequence corresponding to the sense strand sequence). In certainembodiments, for a DsiRNAmm that possesses a mismatched base pairnucleotide at any of positions 3, 4, 5, 6, 7, 8 or 9 of the sensestrand, the corresponding mismatched base pair nucleotide of theantisense strand not only forms a mismatched base pair with the DsiRNAmmsense strand sequence, but also forms a mismatched base pair with aDsiRNAmm target MYC RNA sequence (thus, complementarity between theantisense strand sequence and the sense strand sequence is disrupted atthe mismatched base pair within the DsiRNAmm, and complementarity issimilarly disrupted between the antisense strand sequence of theDsiRNAmm and the target MYC RNA sequence). In alternative embodiments,the mismatch base pair nucleotide of the antisense strand of a DsiRNAmmonly form a mismatched base pair with a corresponding nucleotide of thesense strand sequence of the DsiRNAmm, yet base pairs with itscorresponding target MYC RNA sequence nucleotide (thus, complementaritybetween the antisense strand sequence and the sense strand sequence isdisrupted at the mismatched base pair within the DsiRNAmm, yetcomplementarity is maintained between the antisense strand sequence ofthe DsiRNAmm and the target MYC RNA sequence).

A DsiRNAmm of the invention that possesses a single mismatched base pairwithin the mismatch-tolerant region (mismatch region) as described above(e.g., a DsiRNAmm harboring a mismatched nucleotide residue at any oneof positions 3, 4, 5, 6, 7, 8 or 9 of the sense strand) can furtherinclude one, two or even three additional mismatched base pairs. Inpreferred embodiments, these one, two or three additional mismatchedbase pairs of the DsiRNAmm occur at position(s) 3, 4, 5, 6, 7, 8 and/or9 of the sense strand (and at corresponding residues of the antisensestrand). In one embodiment where one additional mismatched base pair ispresent within a DsiRNAmm, the two mismatched base pairs of the sensestrand can occur, e.g., at nucleotides of both position 4 and position 6of the sense strand (with mismatch also occurring at correspondingnucleotide residues of the antisense strand).

In DsiRNAmm agents possessing two mismatched base pairs, mismatches canoccur consecutively (e.g., at consecutive positions along the sensestrand nucleotide sequence). Alternatively, nucleotides of the sensestrand that form mismatched base pairs with the antisense strandsequence can be interspersed by nucleotides that base pair with theantisense strand sequence (e.g., for a DsiRNAmm possessing mismatchednucleotides at positions 3 and 6, but not at positions 4 and 5, themismatched residues of sense strand positions 3 and 6 are interspersedby two nucleotides that form matched base pairs with correspondingresidues of the antisense strand). For example, two residues of thesense strand (located within the mismatch-tolerant region of the sensestrand) that form mismatched base pairs with the corresponding antisensestrand sequence can occur with zero, one, two, three, four or fivematched base pairs located between these mismatched base pairs.

For certain DsiRNAmm agents possessing three mismatched base pairs,mismatches can occur consecutively (e.g., in a triplet along the sensestrand nucleotide sequence). Alternatively, nucleotides of the sensestrand that form mismatched base pairs with the antisense strandsequence can be interspersed by nucleotides that form matched base pairswith the antisense strand sequence (e.g., for a DsiRNAmm possessingmismatched nucleotides at positions 3, 4 and 8, but not at positions 5,6 and 7, the mismatched residues of sense strand positions 3 and 4 areadjacent to one another, while the mismatched residues of sense strandpositions 4 and 8 are interspersed by three nucleotides that formmatched base pairs with corresponding residues of the antisense strand).For example, three residues of the sense strand (located within themismatch-tolerant region of the sense strand) that form mismatched basepairs with the corresponding antisense strand sequence can occur withzero, one, two, three or four matched base pairs located between any twoof these mismatched base pairs.

For certain DsiRNAmm agents possessing four mismatched base pairs,mismatches can occur consecutively (e.g., in a quadruplet along thesense strand nucleotide sequence). Alternatively, nucleotides of thesense strand that form mismatched base pairs with the antisense strandsequence can be interspersed by nucleotides that form matched base pairswith the antisense strand sequence (e.g., for a DsiRNAmm possessingmismatched nucleotides at positions 3, 5, 7 and 8, but not at positions4 and 6, the mismatched residues of sense strand positions 7 and 8 areadjacent to one another, while the mismatched residues of sense strandpositions 3 and 5 are interspersed by one nucleotide that forms amatched base pair with the corresponding residue of the antisensestrand—similarly, the mismatched residues of sense strand positions 5and 7 are also interspersed by one nucleotide that forms a matched basepair with the corresponding residue of the antisense strand). Forexample, four residues of the sense strand (located within themismatch-tolerant region of the sense strand) that form mismatched basepairs with the corresponding antisense strand sequence can occur withzero, one, two or three matched base pairs located between any two ofthese mismatched base pairs.

In another embodiment, for example with numbering also as depicted inFIG. 1, a DsiRNAmm of the invention comprises a mismatch tolerant regionwhich possesses a single mismatched base pair nucleotide at any one ofpositions 17, 18, 19, 20, 21, 22 or 23 of the antisense strand of theDsiRNA (where position 1 is the 5′ terminal nucleotide of the antisensestrand and position 17 is the nucleotide residue of the antisense strandthat is immediately 3′ (downstream) in the antisense strand of theprojected Ago2 cut site of the target MYC RNA sequence sufficientlycomplementary to the antisense strand sequence). In certain embodiments,for a DsiRNAmm that possesses a mismatched base pair nucleotide at anyof positions 17, 18, 19, 20, 21, 22 or 23 of the antisense strand withrespect to the sense strand of the DsiRNAmm, the mismatched base pairnucleotide of the antisense strand not only forms a mismatched base pairwith the DsiRNAmm sense strand sequence, but also forms a mismatchedbase pair with a DsiRNAmm target MYC RNA sequence (thus, complementaritybetween the antisense strand sequence and the sense strand sequence isdisrupted at the mismatched base pair within the DsiRNAmm, andcomplementarity is similarly disrupted between the antisense strandsequence of the DsiRNAmm and the target MYC RNA sequence). Inalternative embodiments, the mismatch base pair nucleotide of theantisense strand of a DsiRNAmm only forms a mismatched base pair with acorresponding nucleotide of the sense strand sequence of the DsiRNAmm,yet base pairs with its corresponding target MYC RNA sequence nucleotide(thus, complementarity between the antisense strand sequence and thesense strand sequence is disrupted at the mismatched base pair withinthe DsiRNAmm, yet complementarity is maintained between the antisensestrand sequence of the DsiRNAmm and the target MYC RNA sequence).

A DsiRNAmm of the invention that possesses a single mismatched base pairwithin the mismatch-tolerant region as described above (e.g., a DsiRNAmmharboring a mismatched nucleotide residue at positions 17, 18, 19, 20,21, 22 or 23 of the antisense strand) can further include one, two oreven three additional mismatched base pairs. In preferred embodiments,these one, two or three additional mismatched base pairs of the DsiRNAmmoccur at position(s) 17, 18, 19, 20, 21, 22 and/or 23 of the antisensestrand (and at corresponding residues of the sense strand). In oneembodiment where one additional mismatched base pair is present within aDsiRNAmm, the two mismatched base pairs of the antisense strand canoccur, e.g., at nucleotides of both position 18 and position 20 of theantisense strand (with mismatch also occurring at correspondingnucleotide residues of the sense strand).

In DsiRNAmm agents possessing two mismatched base pairs, mismatches canoccur consecutively (e.g., at consecutive positions along the antisensestrand nucleotide sequence). Alternatively, nucleotides of the antisensestrand that form mismatched base pairs with the sense strand sequencecan be interspersed by nucleotides that base pair with the sense strandsequence (e.g., for a DsiRNAmm possessing mismatched nucleotides atpositions 17 and 20, but not at positions 18 and 19, the mismatchedresidues of antisense strand positions 17 and 20 are interspersed by twonucleotides that form matched base pairs with corresponding residues ofthe sense strand). For example, two residues of the antisense strand(located within the mismatch-tolerant region of the sense strand) thatform mismatched base pairs with the corresponding sense strand sequencecan occur with zero, one, two, three, four, five, six or seven matchedbase pairs located between these mismatched base pairs.

For certain DsiRNAmm agents possessing three mismatched base pairs,mismatches can occur consecutively (e.g., in a triplet along theantisense strand nucleotide sequence). Alternatively, nucleotides of theantisense strand that form mismatched base pairs with the sense strandsequence can be interspersed by nucleotides that form matched base pairswith the sense strand sequence (e.g., for a DsiRNAmm possessingmismatched nucleotides at positions 17, 18 and 22, but not at positions19, 20 and 21, the mismatched residues of antisense strand positions 17and 18 are adjacent to one another, while the mismatched residues ofantisense strand positions 18 and 122 are interspersed by threenucleotides that form matched base pairs with corresponding residues ofthe sense strand). For example, three residues of the antisense strand(located within the mismatch-tolerant region of the antisense strand)that form mismatched base pairs with the corresponding sense strandsequence can occur with zero, one, two, three, four, five or six matchedbase pairs located between any two of these mismatched base pairs.

For certain DsiRNAmm agents possessing four mismatched base pairs,mismatches can occur consecutively (e.g., in a quadruplet along theantisense strand nucleotide sequence). Alternatively, nucleotides of theantisense strand that form mismatched base pairs with the sense strandsequence can be interspersed by nucleotides that form matched base pairswith the sense strand sequence (e.g., for a DsiRNAmm possessingmismatched nucleotides at positions 18, 20, 22 and 23, but not atpositions 19 and 21, the mismatched residues of antisense strandpositions 22 and 23 are adjacent to one another, while the mismatchedresidues of antisense strand positions 18 and 20 are interspersed by onenucleotide that forms a matched base pair with the corresponding residueof the sense strand—similarly, the mismatched residues of antisensestrand positions 20 and 22 are also interspersed by one nucleotide thatforms a matched base pair with the corresponding residue of the sensestrand). For example, four residues of the antisense strand (locatedwithin the mismatch-tolerant region of the antisense strand) that formmismatched base pairs with the corresponding sense strand sequence canoccur with zero, one, two, three, four or five matched base pairslocated between any two of these mismatched base pairs.

For reasons of clarity, the location(s) of mismatched nucleotideresidues within the above DsiRNAmm agents are numbered in reference tothe 5′ terminal residue of either sense or antisense strands of theDsiRNAmm. The numbering of positions located within themismatch-tolerant region (mismatch region) of the antisense strand canshift with variations in the proximity of the 5′ terminus of the senseor antisense strand to the projected Ago2 cleavage site. Thus, thelocation(s) of preferred mismatch sites within either antisense strandor sense strand can also be identified as the permissible proximity ofsuch mismatches to the projected Ago2 cut site. Accordingly, in onepreferred embodiment, the position of a mismatch nucleotide of the sensestrand of a DsiRNAmm is the nucleotide residue of the sense strand thatis located immediately 5′ (upstream) of the projected Ago2 cleavage siteof the corresponding target MYC RNA sequence. In other preferredembodiments, a mismatch nucleotide of the sense strand of a DsiRNAmm ispositioned at the nucleotide residue of the sense strand that is locatedtwo nucleotides 5′ (upstream) of the projected Ago2 cleavage site, threenucleotides 5′ (upstream) of the projected Ago2 cleavage site, fournucleotides 5′ (upstream) of the projected Ago2 cleavage site, fivenucleotides 5′ (upstream) of the projected Ago2 cleavage site, sixnucleotides 5′ (upstream) of the projected Ago2 cleavage site, sevennucleotides 5′ (upstream) of the projected Ago2 cleavage site, eightnucleotides 5′ (upstream) of the projected Ago2 cleavage site, or ninenucleotides 5′ (upstream) of the projected Ago2 cleavage site.

Exemplary single mismatch-containing 25/27mer DsiRNAs (DsiRNAmm) includethe following structures (such mismatch-containing structures may alsobe incorporated into other exemplary DsiRNA structures shown herein).

5′-XX^(M)XXXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXX_(M)XXXXXXXXXXXXXXXXXXXXXX-5′5′-XXX^(M)XXXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXX_(M)XXXXXXXXXXXXXXXXXXXXX-5′5′-XXXX^(M)XXXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXX_(M)XXXXXXXXXXXXXXXXXXXX-5′5′-XXXXX^(M)XXXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXX_(M)XXXXXXXXXXXXXXXXXXX-5′5′-XXXXXX^(M)XXXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXX_(M)XXXXXXXXXXXXXXXXXX-5′5′-XXXXXXX^(M)XXXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXX_(M)XXXXXXXXXXXXXXXXX-5′5′-XXXXXXXX^(M)XXXXXXXXXXXXXXDD-3′ 3′-XXXXXXXXXX_(M)XXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “D”=DNA and “M”=Nucleic acid residues (RNA, DNA ornon-natural or modified nucleic acids) that do not base pair (hydrogenbond) with corresponding “M” residues of otherwise complementary strandwhen strands are annealed. Any of the residues of such agents canoptionally be 2′-O-methyl RNA monomers—alternating positioning of2′-O-methyl RNA monomers that commences from the 3′-terminal residue ofthe bottom (second) strand, as shown above, can also be used in theabove DsiRNAmm agents. For the above mismatch structures, the top strandis the sense strand, and the bottom strand is the antisense strand.

In certain embodiments, a DsiRNA of the invention can contain mismatchesthat exist in reference to the target MYC RNA sequence yet do notnecessarily exist as mismatched base pairs within the two strands of theDsiRNA—thus, a DsiRNA can possess perfect complementarity between firstand second strands of a DsiRNA, yet still possess mismatched residues inreference to a target MYC RNA (which, in certain embodiments, may beadvantageous in promoting efficacy and/or potency and/or duration ofeffect). In certain embodiments, where mismatches occur betweenantisense strand and target MYC RNA sequence, the position of a mismatchis located within the antisense strand at a position(s) that correspondsto a sequence of the sense strand located 5′ of the projected Ago2 cutsite of the target region—e.g., antisense strand residue(s) positionedwithin the antisense strand to the 3′ of the antisense residue which iscomplementary to the projected Ago2 cut site of the target sequence.

Exemplary 25/27mer DsiRNAs that harbor a single mismatched residue inreference to target sequences include the following structures.

Target RNA Sequence: 5′-...AXXXXXXXXXXXXXXXXXXXX...-3′DsiRNAmm Sense Strand: 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′DsiRNAmm Antisense Strand: 3′-EXXXXXXXXXXXXXXXXXXXXXXXXXX-5′Target RNA Sequence: 5′-...XAXXXXXXXXXXXXXXXXXXX...-3′DsiRNAmm Sense Strand: 5′-XXXXXXXXXXXXXXXXXXXXXXXDD-3′DsiRNAmm Antisense Strand: 3′-XEXXXXXXXXXXXXXXXXXXXXXXXXX-5′Target RNA Sequence: 5′-...AXXXXXXXXXXXXXXXXXX...-3′DsiRNAmm Sense Strand: 5′-BXXXXXXXXXXXXXXXXXXXXXXDD-3′DsiRNAmm Antisense Strand: 3′-XXEXXXXXXXXXXXXXXXXXXXXXXXX-5′Target RNA Sequence: 5′-...XAXXXXXXXXXXXXXXXXX...-3′DsiRNAmm Sense Strand: 5′-XBXXXXXXXXXXXXXXXXXXXXXDD-3′DsiRNAmm Antisense Strand: 3′-XXXEXXXXXXXXXXXXXXXXXXXXXXX-5′Target RNA Sequence: 5′-...XXAXXXXXXXXXXXXXXXX...-3′DsiRNAmm Sense Strand: 5′-XXBXXXXXXXXXXXXXXXXXXXXDD-3′DsiRNAmm Antisense Strand: 3′-XXXXEXXXXXXXXXXXXXXXXXXXXXX-5′Target RNA Sequence: 5′-...XXXAXXXXXXXXXXXXXXX...-3′DsiRNAmm Sense Strand: 5′-XXXBXXXXXXXXXXXXXXXXXXXDD-3′DsiRNAmm Antisense Strand: 3′-XXXXXEXXXXXXXXXXXXXXXXXXXXX-5′Target RNA Sequence: 5′-...XXXXAXXXXXXXXXXXXXX...-3′DsiRNAmm Sense Strand: 5′-XXXXBXXXXXXXXXXXXXXXXXXDD-3′DsiRNAmm Antisense Strand: 3′-XXXXXXEXXXXXXXXXXXXXXXXXXXX-5′Target RNA Sequence: 5′-...XXXXXAXXXXXXXXXXXXX...-3′DsiRNAmm Sense Strand: 5′-XXXXXBXXXXXXXXXXXXXXXXXDD-3′DsiRNAmm Antisense Strand: 3′-XXXXXXXEXXXXXXXXXXXXXXXXXXX-5′Target RNA Sequence: 5′-...XXXXXXAXXXXXXXXXXXX...-3′DsiRNAmm Sense Strand: 5′-XXXXXXBXXXXXXXXXXXXXXXXDD-3′DsiRNAmm Antisense Strand: 3′-XXXXXXXXEXXXXXXXXXXXXXXXXXX-5′Target RNA Sequence: 5′-...XXXXXXXAXXXXXXXXXXX...-3′DsiRNAmm Sense Strand: 5′-XXXXXXXBXXXXXXXXXXXXXXXDD-3′DsiRNAmm Antisense Strand: 3′-XXXXXXXXXEXXXXXXXXXXXXXXXXX-5′Target RNA Sequence: 5′-...XXXXXXXXAXXXXXXXXXX...-3′DsiRNAmm Sense Strand: 5′-XXXXXXXXBXXXXXXXXXXXXXXDD-3′DsiRNAmm Antisense Strand: 3′-XXXXXXXXXXEXXXXXXXXXXXXXXXX-5′wherein “X”=RNA, “D”=DNA and “E”=Nucleic acid residues (RNA, DNA ornon-natural or modified nucleic acids) that do not base pair (hydrogenbond) with corresponding “A” RNA residues of otherwise complementary(target) strand when strands are annealed, yet optionally do base pairwith corresponding “B” residues (“B” residues are also RNA, DNA ornon-natural or modified nucleic acids). Any of the residues of suchagents can optionally be 2′-O-methyl RNA monomers—alternatingpositioning of 2′-O-methyl RNA monomers that commences from the3′-terminal residue of the bottom (second) strand, as shown above, canalso be used in the above DsiRNA agents.

In certain embodiments, the guide strand of a dsRNA of the inventionthat is sufficiently complementary to a target RNA (e.g., mRNA) along atleast 19 nucleotides of the target gene sequence to reduce target geneexpression is not perfectly complementary to the at least 19 nucleotidelong target gene sequence. Rather, it is appreciated that the guidestrand of a dsRNA of the invention that is sufficiently complementary toa target mRNA along at least 19 nucleotides of a target RNA sequence toreduce target gene expression can have one, two, three, or even four ormore nucleotides that are mismatched with the 19 nucleotide or longertarget strand sequence. Thus, for a 19 nucleotide target RNA sequence,the guide strand of a dsRNA of the invention can be sufficientlycomplementary to the target RNA sequence to reduce target gene levelswhile possessing, e.g., only 15/19, 16/19, 17/19 or 18/19 matchednucleotide residues between guide strand and target RNA sequence.

In addition to the above-exemplified structures, dsRNAs of the inventioncan also possess one, two or three additional residues that form furthermismatches with the target MYC RNA sequence. Such mismatches can beconsecutive, or can be interspersed by nucleotides that form matchedbase pairs with the target MYC RNA sequence. Where interspersed bynucleotides that form matched base pairs, mismatched residues can bespaced apart from each other within a single strand at an interval ofone, two, three, four, five, six, seven or even eight base pairednucleotides between such mismatch-forming residues.

As for the above-described DsiRNAmm agents, a preferred location withindsRNAs (e.g., DsiRNAs) for antisense strand nucleotides that formmismatched base pairs with target MYC RNA sequence (yet may or may notform mismatches with corresponding sense strand nucleotides) is withinthe antisense strand region that is located 3′ (downstream) of theantisense strand sequence which is complementary to the projected Ago2cut site of the DsiRNA (e.g., in FIG. 1, the region of the antisensestrand which is 3′ of the projected Ago2 cut site is preferred formismatch-forming residues and happens to be located at positions 17-23of the antisense strand for the 25/27mer agent shown in FIG. 1). Thus,in one embodiment, the position of a mismatch nucleotide (in relation tothe target MYC RNA sequence) of the antisense strand of a DsiRNAmm isthe nucleotide residue of the antisense strand that is locatedimmediately 3′ (downstream) within the antisense strand sequence of theprojected Ago2 cleavage site of the corresponding target MYC RNAsequence. In other preferred embodiments, a mismatch nucleotide of theantisense strand of a DsiRNAmm (in relation to the target MYC RNAsequence) is positioned at the nucleotide residue of the antisensestrand that is located two nucleotides 3′ (downstream) of thecorresponding projected Ago2 cleavage site, three nucleotides 3′(downstream) of the corresponding projected Ago2 cleavage site, fournucleotides 3′ (downstream) of the corresponding projected Ago2 cleavagesite, five nucleotides 3′ (downstream) of the corresponding projectedAgo2 cleavage site, six nucleotides 3′ (downstream) of the projectedAgo2 cleavage site, seven nucleotides 3′ (downstream) of the projectedAgo2 cleavage site, eight nucleotides 3′ (downstream) of the projectedAgo2 cleavage site, or nine nucleotides 3′ (downstream) of the projectedAgo2 cleavage site.

In dsRNA agents possessing two mismatch-forming nucleotides of theantisense strand (where mismatch-forming nucleotides are mismatchforming in relation to target MYC RNA sequence), mismatches can occurconsecutively (e.g., at consecutive positions along the antisense strandnucleotide sequence). Alternatively, nucleotides of the antisense strandthat form mismatched base pairs with the target MYC RNA sequence can beinterspersed by nucleotides that base pair with the target MYC RNAsequence (e.g., for a DsiRNA possessing mismatch-forming nucleotides atpositions 17 and 20 (starting from the 5′ terminus (position 1) of theantisense strand of the 25/27mer agent shown in FIG. 1), but not atpositions 18 and 19, the mismatched residues of sense strand positions17 and 20 are interspersed by two nucleotides that form matched basepairs with corresponding residues of the target MYC RNA sequence). Forexample, two residues of the antisense strand (located within themismatch-tolerant region of the antisense strand) that form mismatchedbase pairs with the corresponding target MYC RNA sequence can occur withzero, one, two, three, four or five matched base pairs (with respect totarget MYC RNA sequence) located between these mismatch-forming basepairs.

For certain dsRNAs possessing three mismatch-forming base pairs(mismatch-forming with respect to target MYC RNA sequence),mismatch-forming nucleotides can occur consecutively (e.g., in a tripletalong the antisense strand nucleotide sequence). Alternatively,nucleotides of the antisense strand that form mismatched base pairs withthe target MYC RNA sequence can be interspersed by nucleotides that formmatched base pairs with the target MYC RNA sequence (e.g., for a DsiRNApossessing mismatched nucleotides at positions 17, 18 and 22, but not atpositions 19, 20 and 21, the mismatch-forming residues of antisensestrand positions 17 and 18 are adjacent to one another, while themismatch-forming residues of antisense strand positions 18 and 22 areinterspersed by three nucleotides that form matched base pairs withcorresponding residues of the target MYC RNA). For example, threeresidues of the antisense strand (located within the mismatch-tolerantregion of the antisense strand) that form mismatched base pairs with thecorresponding target MYC RNA sequence can occur with zero, one, two,three or four matched base pairs located between any two of thesemismatch-forming base pairs.

For certain dsRNAs possessing four mismatch-forming base pairs(mismatch-forming with respect to target MYC RNA sequence),mismatch-forming nucleotides can occur consecutively (e.g., in aquadruplet along the sense strand nucleotide sequence). Alternatively,nucleotides of the antisense strand that form mismatched base pairs withthe target MYC RNA sequence can be interspersed by nucleotides that formmatched base pairs with the target MYC RNA sequence (e.g., for a DsiRNApossessing mismatch-forming nucleotides at positions 17, 19, 21 and 22,but not at positions 18 and 20, the mismatch-forming residues ofantisense strand positions 21 and 22 are adjacent to one another, whilethe mismatch-forming residues of antisense strand positions 17 and 19are interspersed by one nucleotide that forms a matched base pair withthe corresponding residue of the target MYC RNA sequence—similarly, themismatch-forming residues of antisense strand positions 19 and 21 arealso interspersed by one nucleotide that forms a matched base pair withthe corresponding residue of the target MYC RNA sequence). For example,four residues of the antisense strand (located within themismatch-tolerant region of the antisense strand) that form mismatchedbase pairs with the corresponding target MYC RNA sequence can occur withzero, one, two or three matched base pairs located between any two ofthese mismatch-forming base pairs.

The above DsiRNAmm and other dsRNA structures are described in order toexemplify certain structures of DsiRNAmm and dsRNA agents. Design of theabove DsiRNAmm and dsRNA structures can be adapted to generate, e.g.,DsiRNAmm forms of other DsiRNA structures shown infra. As exemplifiedabove, dsRNAs can also be designed that possess single mismatches (ortwo, three or four mismatches) between the antisense strand of the dsRNAand a target sequence, yet optionally can retain perfect complementaritybetween sense and antisense strand sequences of a dsRNA.

It is further noted that the dsRNA agents exemplified infra can alsopossess insertion/deletion (in/del) structures within theirdouble-stranded and/or target MYC RNA-aligned structures. Accordingly,the dsRNAs of the invention can be designed to possess in/del variationsin, e.g., antisense strand sequence as compared to target MYC RNAsequence and/or antisense strand sequence as compared to sense strandsequence, with preferred location(s) for placement of such in/delnucleotides corresponding to those locations described above forpositioning of mismatched and/or mismatch-forming base pairs.

It is also noted that the DsiRNAs of the instant invention can toleratemismatches within the 3′-terminal region of the sense strand/5′-terminalregion of the antisense strand, as this region is modeled to beprocessed by Dicer and liberated from the guide strand sequence thatloads into RISC. Exemplary DsiRNA structures of the invention thatharbor such mismatches include the following:

Target RNA Sequence: 5′-...XXXXXXXXXXXXXXXXXXXXXHXXX...-3′DsiRNA Sense Strand: 5′-XXXXXXXXXXXXXXXXXXXXXIXDD-3′DsiRNA Antisense Strand: 3′-XXXXXXXXXXXXXXXXXXXXXXXJXXX-5′Target RNA Sequence: 5′-...XXXXXXXXXXXXXXXXXXXXXXHXX...-3′DsiRNA Sense Strand: 5′-XXXXXXXXXXXXXXXXXXXXXXIDD-3′DsiRNA Antisense Strand: 3′-XXXXXXXXXXXXXXXXXXXXXXXXJXX-5′Target RNA Sequence: 5′-...XXXXXXXXXXXXXXXXXXXXXXXHX...-3′DsiRNA Sense Strand: 5′-XXXXXXXXXXXXXXXXXXXXXXXID-3′DsiRNA Antisense Strand: 3′-XXXXXXXXXXXXXXXXXXXXXXXXXJX-5′Target RNA Sequence: 5′-...XXXXXXXXXXXXXXXXXXXXXXXXH...-3′DsiRNA Sense Strand: 5′-XXXXXXXXXXXXXXXXXXXXXXXDI-3′DsiRNA Antisense Strand: 3′-XXXXXXXXXXXXXXXXXXXXXXXXXXJ-5′wherein “X”=RNA, “D”=DNA and “I” and “J”=Nucleic acid residues (RNA, DNAor non-natural or modified nucleic acids) that do not base pair(hydrogen bond) with one another, yet optionally “J” is complementary totarget RNA sequence nucleotide “H”. Any of the residues of such agentscan optionally be 2′-O-methyl RNA monomers—alternating positioning of2′-O-methyl RNA monomers that commences from the 3′-terminal residue ofthe bottom (second) strand, as shown above—or any of the above-describedmethylation patterns—can also be used in the above DsiRNA agents. Theabove mismatches can also be combined within the DsiRNAs of the instantinvention.

In the below structures, such mismatches are introduced within theasymmetric MYC-622 DsiRNA (newly-introduced mismatch residues areitalicized):

MYC-622 25/27mer DsiRNA, mismatch position=19 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 19 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-622 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-622 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 21 of the sensestrand is alternatively ‘U’ or ‘G’.MYC-622 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 22 of the sensestrand is alternatively ‘A’ or ‘C’.MYC-622 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 23 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-622 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘t’ residue of position 24 of the sensestrand is alternatively ‘a’ or ‘g’.MYC-622 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘a’ residue of position 25 of the sensestrand is alternatively ‘c’ or ‘g’.MYC-622 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 1 of the antisensestrand is alternatively ‘G’ or ‘C’.MYC-622 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 2 of the antisensestrand is alternatively ‘U’ or ‘C’.MYC-622 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 3 of the antisensestrand is alternatively ‘C’ or ‘G’.

MYC-622 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 4 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-622 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 5 of the antisensestrand is alternatively ‘A’ or ‘C’.MYC-622 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-622 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 7 of the antisensestrand is alternatively ‘C’ or ‘G’.

As another example, in the below structures, such mismatches areintroduced within the asymmetric MYC-953 DsiRNA (newly-introducedmismatch residues are italicized):

MYC-953 25/27mer DsiRNA, mismatch position=19 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 19 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-953 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-953 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 21 of the sensestrand is alternatively ‘G’ or ‘C’.MYC-953 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘G’ residue of position 22 of the sensestrand is alternatively ‘U’ or ‘C’.MYC-953 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 23 of the sensestrand is alternatively ‘U’ or ‘G’.MYC-953 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘g’ residue of position 24 of the sensestrand is alternatively ‘t’ or ‘c’.MYC-953 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘a’ residue of position 25 of the sensestrand is alternatively ‘c’ or ‘c’.MYC-953 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 1 of the antisensestrand is alternatively ‘G’ or ‘C’.MYC-953 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘C’ residue of position 2 of the antisensestrand is alternatively ‘A’ or ‘G’.MYC-953 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 3 of the antisensestrand is alternatively ‘A’ or ‘C’.MYC-953 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘C’ residue of position 4 of the antisensestrand is alternatively ‘A’ or ‘G’.MYC-953 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 5 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-953 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-953 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 7 of the antisensestrand is alternatively ‘C’ or ‘G’.

As an additional example, in the below structures, such mismatches areintroduced within the asymmetric MYC-1364 DsiRNA (newly-introducedmismatch residues are italicized):

MYC-1364 25/27mer DsiRNA, mismatch position=19 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 19 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1364 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1364 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 21 of the sensestrand is alternatively ‘U’ or ‘C’.MYC-1364 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘G’ residue of position 22 of the sensestrand is alternatively ‘A’ or ‘C’.MYC-1364 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 23 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1364 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘t’ residue of position 24 of the sensestrand is alternatively ‘a’ or ‘c’.MYC-1364 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘a’ residue of position 25 of the sensestrand is alternatively ‘c’ or ‘g’.MYC-1364 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 1 of the antisensestrand is alternatively ‘G’ or ‘C’.MYC-1364 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 2 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-1364 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 3 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-1364 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘C’ residue of position 4 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-1364 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 5 of the antisensestrand is alternatively ‘A’ or ‘G’.MYC-1364 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-1364 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 7 of the antisensestrand is alternatively ‘C’ or ‘G’.

As a further example, in the below structures, such mismatches areintroduced within the asymmetric MYC-1370 DsiRNA (newly-introducedmismatch residues are italicized):

MYC-1370 25/27mer DsiRNA, mismatch position=19 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 19 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1370 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1370 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 21 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1370 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 22 of the sensestrand is alternatively ‘A’ or ‘G’.MYC-1370 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 23 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1370 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘t’ residue of position 24 of the sensestrand is alternatively ‘a’ or ‘c’.MYC-1370 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘a’ residue of position 25 of the sensestrand is alternatively ‘c’ or

‘g’.

MYC-1370 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 1 of the antisensestrand is alternatively ‘G’ or ‘C’.MYC-1370 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 2 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-1370 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 3 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-1370 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 4 of the antisensestrand is alternatively ‘U’ or ‘C’.

MYC-1370 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 5 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-1370 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-1370 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 7 of the antisensestrand is alternatively ‘C’ or ‘G’.

As another example, in the below structures, such mismatches areintroduced within the asymmetric MYC-1711 DsiRNA (newly-introducedmismatch residues are italicized):

MYC-1711 25/27mer DsiRNA, mismatch position=19 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 19 of the sensestrand is alternatively ‘U’ or ‘C’.MYC-1711 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1711 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 21 of the sensestrand is alternatively ‘U’ or ‘G’.MYC-1711 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 22 of the sensestrand is alternatively ‘A’ or ‘G’.MYC-1711 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 23 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1711 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘t’ residue of position 24 of the sensestrand is alternatively ‘a’ or ‘c’.MYC-1711 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘t’ residue of position 25 of the sensestrand is alternatively ‘c’ or ‘g’.MYC-1711 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 1 of the antisensestrand is alternatively ‘G’ or ‘C’.MYC-1711 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 2 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-1711 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 3 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-1711 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 4 of the antisensestrand is alternatively ‘U’ or ‘C’.MYC-1711 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 5 of the antisensestrand is alternatively ‘A’ or ‘C’.MYC-1711 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-1711 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 7 of the antisensestrand is alternatively ‘A’ or ‘G’.

As an additional example, in the below structures, such mismatches areintroduced within the asymmetric MYC-1769 DsiRNA (newly-introducedmismatch residues are italicized):

MYC-1769 25/27mer DsiRNA, mismatch position=19 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 19 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1769 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1769 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 21 of the sensestrand is alternatively ‘U’ or ‘C’.MYC-1769 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 22 of the sensestrand is alternatively ‘A’ or ‘G’.MYC-1769 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 23 of the sensestrand is alternatively ‘U’ or ‘G’.MYC-1769 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘g’ residue of position 24 of the sensestrand is alternatively ‘t’ or ‘c’.MYC-1769 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘a’ residue of position 25 of the sensestrand is alternatively ‘t’ or ‘g’.MYC-1769 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 1 of the antisensestrand is alternatively ‘A’ or ‘C’.MYC-1769 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘C’ residue of position 2 of the antisensestrand is alternatively ‘A’ or ‘G’.MYC-1769 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 3 of the antisensestrand is alternatively ‘A’ or ‘C’.MYC-1769 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 4 of the antisensestrand is alternatively ‘U’ or ‘C’.MYC-1769 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 5 of the antisensestrand is alternatively ‘A’ or ‘G’.MYC-1769 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-1769 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 7 of the antisensestrand is alternatively ‘C’ or ‘G’.

As a further example, in the below structures, such mismatches areintroduced within the asymmetric MYC-1965 DsiRNA (newly-introducedmismatch residues are italicized): MYC-1965 25/27mer DsiRNA, mismatchposition=19 of sense strand (from 5′-terminus)

Optionally, the mismatched ‘U’ residue of position 19 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1965 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1965 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 21 of the sensestrand is alternatively ‘U’ or ‘C’.MYC-1965 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 22 of the sensestrand is alternatively ‘A’ or ‘G’.MYC-1965 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 23 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-1965 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘g’ residue of position 24 of the sensestrand is alternatively ‘a’ or ‘c’.MYC-1965 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘a’ residue of position 25 of the sensestrand is alternatively ‘t’ or ‘c’.MYC-1965 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 1 of the antisensestrand is alternatively ‘A’ or ‘G’.MYC-1965 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘C’ residue of position 2 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-1965 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 3 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-1965 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 4 of the antisensestrand is alternatively ‘U’ or ‘C’.MYC-1965 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 5 of the antisensestrand is alternatively ‘A’ or ‘G’.MYC-1965 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-1965 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 7 of the antisensestrand is alternatively ‘C’ or ‘G’.

As another example, in the below structures, such mismatches areintroduced within the asymmetric MYC-2099 DsiRNA (newly-introducedmismatch residues are italicized):

MYC-2099 25/27mer DsiRNA, mismatch position=19 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 19 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2099 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2099 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 21 of the sensestrand is alternatively ‘G’ or ‘C’.MYC-2099 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 22 of the sensestrand is alternatively ‘A’ or ‘G’.MYC-2099 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 23 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2099 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘t’ residue of position 24 of the sensestrand is alternatively ‘a’ or ‘c’.MYC-2099 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘t’ residue of position 25 of the sensestrand is alternatively ‘c’ or ‘g’.MYC-2099 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 1 of the antisensestrand is alternatively ‘G’ or ‘C’.MYC-2099 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 2 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-2099 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 3 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2099 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 4 of the antisensestrand is alternatively ‘U’ or ‘C’.MYC-2099 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 5 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2099 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2099 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 7 of the antisensestrand is alternatively ‘C’ or ‘G’.

As an additional example, in the below structures, such mismatches areintroduced within the asymmetric MYC-2115 DsiRNA (newly-introducedmismatch residues are italicized):

MYC-2115 25/27mer DsiRNA, mismatch position=19 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 19 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2115 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2115 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 21 of the sensestrand is alternatively ‘U’ or ‘C’.MYC-2115 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘G’ residue of position 22 of the sensestrand is alternatively ‘U’ or ‘C’.MYC-2115 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 23 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2115 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘g’ residue of position 24 of the sensestrand is alternatively ‘a’ or ‘c’.MYC-2115 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘a’ residue of position 25 of the sensestrand is alternatively ‘c’ or‘g’.MYC-2115 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 1 of the antisensestrand is alternatively ‘G’ or ‘C’.MYC-2115 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘C’ residue of position 2 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-2115 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 3 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2115 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘C’ residue of position 4 of the antisensestrand is alternatively ‘A’ or ‘G’.MYC-2115 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 5 of the antisensestrand is alternatively ‘A’ or ‘G’.MYC-2115 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2115 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 7 of the antisensestrand is alternatively ‘C’ or ‘G’.

As a further example, in the below structures, such mismatches areintroduced within the asymmetric MYC-2120 DsiRNA (newly-introducedmismatch residues are italicized):

MYC-2120 25/27mer DsiRNA, mismatch position=19 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 19 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2120 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2120 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 21 of the sensestrand is alternatively ‘U’ or ‘C’.MYC-2120 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘G’ residue of position 22 of the sensestrand is alternatively ‘A’ or ‘C’.MYC-2120 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 23 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2120 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘g’ residue of position 24 of the sensestrand is alternatively ‘a’ or ‘c’.MYC-2120 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘a’ residue of position 25 of the sensestrand is alternatively ‘c’ or ‘g’.MYC-2120 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 1 of the antisensestrand is alternatively ‘G’ or ‘C’.MYC-2120 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘C’ residue of position 2 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-2120 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 3 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2120 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘C’ residue of position 4 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-2120 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 5 of the antisensestrand is alternatively ‘A’ or ‘G’.MYC-2120 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2120 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 7 of the antisensestrand is alternatively ‘C’ or ‘G’.

As another example, in the below structures, such mismatches areintroduced within the asymmetric MYC-2196 DsiRNA (newly-introducedmismatch residues are italicized): MYC-2196 25/27mer DsiRNA, mismatchposition=19 of sense strand (from 5′-terminus)

Optionally, the mismatched ‘U’ residue of position 19 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2196 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2196 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 21 of the sensestrand is alternatively ‘U’ or ‘G’.MYC-2196 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 22 of the sensestrand is alternatively ‘A’ or ‘C’.MYC-2196 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 23 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2196 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘g’ residue of position 24 of the sensestrand is alternatively ‘a’ or ‘c’.MYC-2196 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘a’ residue of position 25 of the sensestrand is alternatively ‘c’ or ‘g’.MYC-2196 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 1 of the antisensestrand is alternatively ‘G’ or ‘C’.MYC-2196 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘C’ residue of position 2 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-2196 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 3 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2196 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 4 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-2196 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 5 of the antisensestrand is alternatively ‘A’ or ‘C’.MYC-2196 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2196 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 7 of the antisensestrand is alternatively ‘C’ or ‘G’.

As an additional example, in the below structures, such mismatches areintroduced within the asymmetric MYC-2233 DsiRNA (newly-introducedmismatch residues are italicized):

MYC-2233 25/27mer DsiRNA, mismatch position=19 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 19 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2233 25/27mer DsiRNA, mismatch position=20 of sense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 20 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2233 25/27mer DsiRNA, mismatch position=21 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 21 of the sensestrand is alternatively ‘G’ or ‘C’.MYC-2233 25/27mer DsiRNA, mismatch position=22 of sense strand (from5′-terminus)

Optionally, the mismatched ‘G’ residue of position 22 of the sensestrand is alternatively ‘A’ or ‘C’.MYC-2233 25/27mer DsiRNA, mismatch position=23 of sense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 23 of the sensestrand is alternatively ‘C’ or ‘G’.MYC-2233 25/27mer DsiRNA, mismatch position=24 of sense strand (from5′-terminus)

Optionally, the mismatched ‘t’ residue of position 24 of the sensestrand is alternatively ‘a’ or ‘c’.MYC-2233 25/27mer DsiRNA, mismatch position=25 of sense strand (from5′-terminus)

Optionally, the mismatched ‘a’ residue of position 25 of the sensestrand is alternatively ‘c’ or ‘g’.MYC-2233 25/27mer DsiRNA, mismatch position=1 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 1 of the antisensestrand is alternatively ‘G’ or ‘C’.MYC-2233 25/27mer DsiRNA, mismatch position=2 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 2 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-2233 25/27mer DsiRNA, mismatch position=3 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 3 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2233 25/27mer DsiRNA, mismatch position=4 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘C’ residue of position 4 of the antisensestrand is alternatively ‘U’ or ‘G’.MYC-2233 25/27mer DsiRNA, mismatch position=5 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 5 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2233 25/27mer DsiRNA, mismatch position=6 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘U’ residue of position 6 of the antisensestrand is alternatively ‘C’ or ‘G’.MYC-2233 25/27mer DsiRNA, mismatch position=7 of antisense strand (from5′-terminus)

Optionally, the mismatched ‘A’ residue of position 7 of the antisensestrand is alternatively ‘C’ or ‘G’.

For the above oligonucleotide strand sequences, it is contemplated thatthe sense strand sequence of one depicted duplex can be combined with anantisense strand of another depicted duplex, thereby forming a distinctduplex—in certain instances, such duplexes contain a mismatched residuewith respect to the MYC target transcript sequence, while such sense andantisense strand sequences do not present a mismatch at this residuewith respect to one another (e.g., duplexes comprising SEQ ID NOs: 3707and 3720; SEQ ID NOs: 3708 and 3719; SEQ ID NOs: 3709 and 3718, etc.,are contemplated as exemplary of such duplexes).

As noted above, introduction of mismatches can be performed upon any ofthe DsiRNAs described herein.

The mismatches of such DsiRNA structures can be combined to produce aDsiRNA possessing, e.g., two, three or even four mismatches within the3′-terminal four to seven nucleotides of the sense strand/5′-terminalfour to seven nucleotides of the antisense strand.

Indeed, in view of the flexibility of sequences which can beincorporated into DsiRNAs at the 3′-terminal residues of the sensestrand/5′-terminal residues of the antisense strand, in certainembodiments, the sequence requirements of an asymmetric DsiRNA of theinstant invention can be represented as the following (minimalist)structure (shown for an exemplary MYC-953 DsiRNA sequence):

(SEQ ID NO: 3875) 5′-ACGACGAGACCUUCAUCAXXXXXX[X]_(n)-3′ (SEQ ID NO:3876) 3′-CCUGCUGCUCUGGAAGUAGUXXXXXX[X]_(n)-5′where n=1 to 5, 1 to 10, 1 to 20, 1 to 30, 1 to 50, or 1 to 80 or more.

MYC-953 mRNA Target: (SEQ ID NO: 3877)5′-GGACGACGAGACCUUCAUCAXXXXXXX-3′.

The MYC target site may also be a site which is targeted by one or moreof several oligonucleotides whose complementary target sites overlapwith a stated target site. For example, for an exemplary MYC-953 DsiRNA,it is noted that certain DsiRNAs targeting overlapping and only slightlyoffset MYC sequences can exhibit activity levels similar to that ofMYC-953 (specifically, see MYC-952 of Table 9 below. Thus, in certainembodiments, a designated target sequence region can be effectivelytargeted by a series of DsiRNAs possessing largely overlappingsequences. (E.g., if considering DsiRNAs of the MYC-952 and MYC-953target site(s), a more encompassing MYC transcript target sequence mightbe recited as, e.g., 5′-CGGACGACGAGACCUUCAUCAAAAACAU-3′ (SEQ ID NO:3878), wherein any given DsiRNA (e.g., a DsiRNA selected from MYC-952and MYC-953) only targets a sub-sequence within such a sequence region,yet the entire sequence can be considered a viable target for such aseries of DsiRNAs).

Additionally and/or alternatively, mismatches within the 3′-terminalseven nucleotides of the sense strand/5′-terminal seven nucleotides ofthe antisense strand can be combined with mismatches positioned at othermismatch-tolerant positions, as described above.

In view of the present identification of the above-described Dicersubstrate agents (DsiRNAs) as inhibitors of MYC levels via targeting ofspecific MYC sequences, it is also recognized that dsRNAs havingstructures similar to those described herein can also be synthesizedwhich target other sequences within the MYC sequence of NM_002467.4 orNM_010849.4, or within variants thereof (e.g., target sequencespossessing 80% identity, 90% identity, 95% identity, 96% identity, 97%identity, 98% identity, 99% or more identity to a sequence ofNM_002467.4 and/or NM_010849.4).

Anti-MYC DsiRNA Design/Synthesis

It has been found empirically that longer dsRNA species of from 25 to 35nucleotides (DsiRNAs) and especially from 25 to 30 nucleotides giveunexpectedly effective results in terms of potency and duration ofaction, as compared to 19-23mer siRNA agents. Without wishing to bebound by the underlying theory of the dsRNA processing mechanism, it isthought that the longer dsRNA species serve as a substrate for the Dicerenzyme in the cytoplasm of a cell. In addition to cleaving the dsRNA ofthe invention into shorter segments, Dicer is thought to facilitate theincorporation of a single-stranded cleavage product derived from thecleaved dsRNA into the RISC complex that is responsible for thedestruction of the cytoplasmic RNA (e.g., MYC RNA) of or derived fromthe target gene, MYC (or other gene associated with a MYC-associateddisease or disorder). Prior studies (Rossi et al., U.S. PatentApplication No. 2007/0265220) have shown that the cleavability of adsRNA species (specifically, a DsiRNA agent) by Dicer corresponds withincreased potency and duration of action of the dsRNA species.

Certain preferred anti-MYC DsiRNA agents were selected from apre-screened population. Design of DsiRNAs can optionally involve use ofpredictive scoring algorithms that perform in silico assessments of theprojected activity/efficacy of a number of possible DsiRNA agentsspanning a region of sequence. Information regarding the design of suchscoring algorithms can be found, e.g., in Gong et al. (BMCBioinformatics 2006, 7:516), though a more recent “v3” algorithmrepresents a theoretically improved algorithm relative to siRNA scoringalgorithms previously available in the art. (E.g., the “v3” and “v4”scoring algorithms are machine learning algorithms that are not reliantupon any biases in human sequence. In addition, the “v3” and “v4”algorithms derive from data sets that are many-fold larger than thatfrom which an older “v2” algorithm such as that described in Gong et al.derives.)

The first and second oligonucleotides of the DsiRNA agents of theinstant invention are not required to be completely complementary. Infact, in one embodiment, the 3′-terminus of the sense strand containsone or more mismatches. In one aspect, two mismatches are incorporatedat the 3′ terminus of the sense strand. In another embodiment, theDsiRNA of the invention is a double stranded RNA molecule containing twoRNA oligonucleotides each of which is 27 nucleotides in length and, whenannealed to each other, have blunt ends and a two nucleotide mismatch onthe 3′-terminus of the sense strand (the 5′-terminus of the antisensestrand). The use of mismatches or decreased thermodynamic stability(specifically at the 3′-sense/5′-antisense position) has been proposedto facilitate or favor entry of the antisense strand into RISC (Schwarzet al., 2003, Cell 115: 199-208; Khvorova et al., 2003, Cell 115:209-216), presumably by affecting some rate-limiting unwinding stepsthat occur with entry of the siRNA into RISC. Thus, terminal basecomposition has been included in design algorithms for selecting active21mer siRNA duplexes (Ui-Tei et al., 2004, Nucleic Acids Res 32:936-948; Reynolds et al., 2004, Nat Biotechnol 22: 326-330). With Dicercleavage of the dsRNA of this embodiment, the small end-terminalsequence which contains the mismatches will either be left unpaired withthe antisense strand (become part of a 3′-overhang) or be cleavedentirely off the final 21-mer siRNA. These “mismatches”, therefore, donot persist as mismatches in the final RNA component of RISC. Thefinding that base mismatches or destabilization of segments at the3′-end of the sense strand of Dicer substrate improved the potency ofsynthetic duplexes in RNAi, presumably by facilitating processing byDicer, was a surprising finding of past works describing the design anduse of 25-30mer dsRNAs (also termed “DsiRNAs” herein; Rossi et al., U.S.Patent Application Nos. 2005/0277610, 2005/0244858 and 2007/0265220).

Modification of Anti-MYC dsRNAs

One major factor that inhibits the effect of double stranded RNAs(“dsRNAs”) is the degradation of dsRNAs (e.g., siRNAs and DsiRNAs) bynucleases. A 3′-exonuclease is the primary nuclease activity present inserum and modification of the 3′-ends of antisense DNA oligonucleotidesis crucial to prevent degradation (Eder et al., 1991, Antisense Res Dev,1: 141-151). An RNase-T family nuclease has been identified called ERI-1which has 3′ to 5′ exonuclease activity that is involved in regulationand degradation of siRNAs (Kennedy et al., 2004, Nature 427: 645-649;Hong et al., 2005, Biochem J, 390: 675-679). This gene is also known asThex1 (NM_02067) in mice or THEX1 (NM_153332) in humans and is involvedin degradation of histone mRNA; it also mediates degradation of3′-overhangs in siRNAs, but does not degrade duplex RNA (Yang et al.,2006, J Biol Chem, 281: 30447-30454). It is therefore reasonable toexpect that 3′-end-stabilization of dsRNAs, including the DsiRNAs of theinstant invention, will improve stability.

XRN1 (NM_019001) is a 5′ to 3′ exonuclease that resides in P-bodies andhas been implicated in degradation of mRNA targeted by miRNA (Rehwinkelet al., 2005, RNA 11: 1640-1647) and may also be responsible forcompleting degradation initiated by internal cleavage as directed by asiRNA. XRN2 (NM_012255) is a distinct 5′ to 3′ exonuclease that isinvolved in nuclear RNA processing.

RNase A is a major endonuclease activity in mammals that degrades RNAs.It is specific for ssRNA and cleaves at the 3′-end of pyrimidine bases.SiRNA degradation products consistent with RNase A cleavage can bedetected by mass spectrometry after incubation in serum (Turner et al.,2007, Mol Biosyst 3: 43-50). The 3′-overhangs enhance the susceptibilityof siRNAs to RNase degradation. Depletion of RNase A from serum reducesdegradation of siRNAs; this degradation does show some sequencepreference and is worse for sequences having poly A/U sequence on theends (Haupenthal et al., 2006 Biochem Pharmacol 71: 702-710). Thissuggests the possibility that lower stability regions of the duplex may“breathe” and offer transient single-stranded species available fordegradation by RNase A. RNase A inhibitors can be added to serum andimprove siRNA longevity and potency (Haupenthal et al., 2007, Int J.Cancer 121: 206-210).

In 21mers, phosphorothioate or boranophosphate modifications directlystabilize the internucleoside phosphate linkage. Boranophosphatemodified RNAs are highly nuclease resistant, potent as silencing agents,and are relatively non-toxic. Boranophosphate modified RNAs cannot bemanufactured using standard chemical synthesis methods and instead aremade by in vitro transcription (IVT) (Hall et al., 2004, Nucleic AcidsRes 32: 5991-6000; Hall et al., 2006, Nucleic Acids Res 34: 2773-2781).Phosphorothioate (PS) modifications can be easily placed in the RNAduplex at any desired position and can be made using standard chemicalsynthesis methods. The PS modification shows dose-dependent toxicity, somost investigators have recommended limited incorporation in siRNAs,favoring the 3′-ends where protection from nucleases is most important(Harborth et al., 2003, Antisense Nucleic Acid Drug Dev 13: 83-105; Chiuand Rana, 2003, Mol Cell 10: 549-561; Braasch et al., 2003, Biochemistry42: 7967-7975; Amarzguioui et al., 2003, Nucleic Acids Research 31:589-595). More extensive PS modification can be compatible with potentRNAi activity; however, use of sugar modifications (such as 2′-O-methylRNA) may be superior (Choung et al., 2006, Biochem Biophys Res Commun342: 919-927).

A variety of substitutions can be placed at the 2′-position of theribose which generally increases duplex stability (T_(m)) and cangreatly improve nuclease resistance. 2′-O-methyl RNA is a naturallyoccurring modification found in mammalian ribosomal RNAs and transferRNAs. 2′-O-methyl modification in siRNAs is known, but the preciseposition of modified bases within the duplex is important to retainpotency and complete substitution of 2′-O-methyl RNA for RNA willinactivate the siRNA. For example, a pattern that employs alternating2′-O-methyl bases can have potency equivalent to unmodified RNA and isquite stable in serum (Choung et al., 2006, Biochem Biophys Res Commun342: 919-927; Czauderna et al., 2003, Nucleic Acids Research 31:2705-2716).

The 2′-fluoro (2′-F) modification is also compatible with dsRNA (e.g.,siRNA and DsiRNA) function; it is most commonly placed at pyrimidinesites (due to reagent cost and availability) and can be combined with2′-O-methyl modification at purine positions; 2′-F purines are availableand can also be used. Heavily modified duplexes of this kind can bepotent triggers of RNAi in vitro (Allerson et al., 2005, J Med Chem 48:901-904; Prakash et al., 2005, J Med Chem 48: 4247-4253; Kraynack andBaker, 2006, RNA 12: 163-176) and can improve performance and extendduration of action when used in vivo (Morrissey et al., 2005, Hepatology41: 1349-1356; Morrissey et al., 2005, Nat Biotechnol 23: 1002-1007). Ahighly potent, nuclease stable, blunt 19mer duplex containingalternative 2′-F and 2′-O-Me bases is taught by Allerson. In thisdesign, alternating 2′-O-Me residues are positioned in an identicalpattern to that employed by Czauderna, however the remaining RNAresidues are converted to 2′-F modified bases. A highly potent, nucleaseresistant siRNA employed by Morrissey employed a highly potent, nucleaseresistant siRNA in vivo. In addition to 2′-O-Me RNA and 2′-F RNA, thisduplex includes DNA, RNA, inverted abasic residues, and a 3′-terminal PSinternucleoside linkage. While extensive modification has certainbenefits, more limited modification of the duplex can also improve invivo performance and is both simpler and less costly to manufacture.Soutschek et al. (2004, Nature 432: 173-178) employed a duplex in vivoand was mostly RNA with two 2′-O-Me RNA bases and limited 3′-terminal PSinternucleoside linkages.

Locked nucleic acids (LNAs) are a different class of 2′-modificationthat can be used to stabilize dsRNA (e.g., siRNA and DsiRNA). Patternsof LNA incorporation that retain potency are more restricted than2′-O-methyl or 2′-F bases, so limited modification is preferred (Braaschet al., 2003, Biochemistry 42: 7967-7975; Grunweller et al., 2003,Nucleic Acids Res 31: 3185-3193; Elmen et al., 2005, Nucleic Acids Res33: 439-447). Even with limited incorporation, the use of LNAmodifications can improve dsRNA performance in vivo and may also alteror improve off target effect profiles (Mook et al., 2007, Mol CancerTher 6: 833-843).

Synthetic nucleic acids introduced into cells or live animals can berecognized as “foreign” and trigger an immune response Immunestimulation constitutes a major class of off-target effects which candramatically change experimental results and even lead to cell death.The innate immune system includes a collection of receptor moleculesthat specifically interact with DNA and RNA that mediate theseresponses, some of which are located in the cytoplasm and some of whichreside in endosomes (Marques and Williams, 2005, Nat Biotechnol 23:1399-1405; Schlee et al., 2006, Mol Ther 14: 463-470). Delivery ofsiRNAs by cationic lipids or liposomes exposes the siRNA to bothcytoplasmic and endosomal compartments, maximizing the risk fortriggering a type 1 interferon (IFN) response both in vitro and in vivo(Morrissey et al., 2005, Nat Biotechnol 23: 1002-1007; Sioud andSorensen, 2003, Biochem Biophys Res Commun 312: 1220-1225; Sioud, 2005,J Mol Biol 348: 1079-1090; Ma et al., 2005, Biochem Biophys Res Commun330: 755-759). RNAs transcribed within the cell are less immunogenic(Robbins et al., 2006, Nat Biotechnol 24: 566-571) and synthetic RNAsthat are immunogenic when delivered using lipid-based methods can evadeimmune stimulation when introduced unto cells by mechanical means, evenin vivo (Heidel et al., 2004, Nat Biotechnol 22: 1579-1582). However,lipid based delivery methods are convenient, effective, and widely used.Some general strategy to prevent immune responses is needed, especiallyfor in vivo application where all cell types are present and the risk ofgenerating an immune response is highest. Use of chemically modifiedRNAs may solve most or even all of these problems.

In certain embodiments, modifications can be included in the anti-MYCdsRNA agents of the present invention so long as the modification doesnot prevent the dsRNA agent from possessing MYC inhibitory activity. Inone embodiment, one or more modifications are made that enhance Dicerprocessing of the DsiRNA agent (an assay for determining Dicerprocessing of a DsiRNA is described elsewhere herein). In a secondembodiment, one or more modifications are made that result in moreeffective MYC inhibition (as described herein, MYC inhibition/MYCinhibitory activity of a dsRNA can be assayed via art-recognized methodsfor determining RNA levels, or for determining MYC polypeptide levels,should such levels be assessed in lieu of or in addition to assessmentof, e.g., MYC mRNA levels). In a third embodiment, one or moremodifications are made that support greater MYC inhibitory activity(means of determining MYC inhibitory activity are described supra). In afourth embodiment, one or more modifications are made that result ingreater potency of MYC inhibitory activity per each dsRNA agent moleculeto be delivered to the cell (potency of MYC inhibitory activity isdescribed supra). Modifications can be incorporated in the 3′-terminalregion, the 5′-terminal region, in both the 3′-terminal and 5′-terminalregion or in some instances in various positions within the sequence.With the restrictions noted above in mind, numbers and combinations ofmodifications can be incorporated into the dsRNA agent. Where multiplemodifications are present, they may be the same or different.Modifications to bases, sugar moieties, the phosphate backbone, andtheir combinations are contemplated. Either 5′-terminus can bephosphorylated.

Examples of modifications contemplated for the phosphate backboneinclude phosphonates, including methylphosphonate, phosphorothioate, andphosphotriester modifications such as alkylphosphotriesters, and thelike. Examples of modifications contemplated for the sugar moietyinclude 2′-alkyl pyrimidine, such as 2′-O-methyl, 2′-fluoro, amino, anddeoxy modifications and the like (see, e.g., Amarzguioui et al., 2003,Nucleic Acids Research 31: 589-595). Examples of modificationscontemplated for the base groups include abasic sugars, 2-O-alkylmodified pyrimidines, 4-thiouracil, 5-bromouracil, 5-iodouracil, and5-(3-aminoallyl)-uracil and the like. Locked nucleic acids, or LNA's,could also be incorporated. Many other modifications are known and canbe used so long as the above criteria are satisfied. Examples ofmodifications are also disclosed in U.S. Pat. Nos. 5,684,143, 5,858,988and 6,291,438 and in U.S. published patent application No. 2004/0203145A1. Other modifications are disclosed in Herdewijn (2000, AntisenseNucleic Acid Drug Dev 10: 297-310), Eckstein (2000, Antisense NucleicAcid Drug Dev 10: 117-21), Rusckowski et al. (2000, Antisense NucleicAcid Drug Dev 10: 333-345), Stein et al. (2001, Antisense Nucleic AcidDrug Dev 11: 317-25); Vorobjev et al. (2001, Antisense Nucleic Acid DrugDev 11: 77-85).

One or more modifications contemplated can be incorporated into eitherstrand. The placement of the modifications in the dsRNA agent cangreatly affect the characteristics of the dsRNA agent, includingconferring greater potency and stability, reducing toxicity, enhanceDicer processing, and minimizing an immune response. In one embodiment,the antisense strand or the sense strand or both strands have one ormore 2′-O-methyl modified nucleotides. In another embodiment, theantisense strand contains 2′-O-methyl modified nucleotides. In anotherembodiment, the antisense stand contains a 3′ overhang that is comprisedof 2′-O-methyl modified nucleotides. The antisense strand could alsoinclude additional 2′-O-methyl modified nucleotides.

In certain embodiments, the anti-MYC DsiRNA agent of the invention hasseveral properties which enhance its processing by Dicer. According tosuch embodiments, the DsiRNA agent has a length sufficient such that itis processed by Dicer to produce an siRNA and at least one of thefollowing properties: (i) the DsiRNA agent is asymmetric, e.g., has a 3′overhang on the sense strand and (ii) the DsiRNA agent has a modified 3′end on the antisense strand to direct orientation of Dicer binding andprocessing of the dsRNA to an active siRNA. According to theseembodiments, the longest strand in the DsiRNA agent comprises 25-30nucleotides. In one embodiment, the sense strand comprises 25-30nucleotides and the antisense strand comprises 25-28 nucleotides. Thus,the resulting dsRNA has an overhang on the 3′ end of the sense strand.The overhang is 1-4 nucleotides, such as 2 nucleotides. The antisensestrand may also have a 5′ phosphate.

In certain embodiments, the sense strand of a DsiRNA agent is modifiedfor Dicer processing by suitable modifiers located at the 3′ end of thesense strand, i.e., the DsiRNA agent is designed to direct orientationof Dicer binding and processing. Suitable modifiers include nucleotidessuch as deoxyribonucleotides, dideoxyribonucleotides, acyclonucleotidesand the like and sterically hindered molecules, such as fluorescentmolecules and the like. Acyclonucleotides substitute a2-hydroxyethoxymethyl group for the 2′-deoxyribofuranosyl sugar normallypresent in dNMPs. Other nucleotide modifiers could include3′-deoxyadenosine (cordycepin), 3′-azido-3′-deoxythymidine (AZT),2′,3′-dideoxyinosine (ddI), 2′,3′-dideoxy-3′-thiacytidine (3TC),2′,3′-didehydro-2′,3′-dideoxythymidine (d4T) and the monophosphatenucleotides of 3′-azido-3′-deoxythymidine (AZT),2′,3′-dideoxy-3′-thiacytidine (3TC) and2′,3′-didehydro-2′,3′-dideoxythymidine (d4T). In one embodiment,deoxynucleotides are used as the modifiers. When nucleotide modifiersare utilized, 1-3 nucleotide modifiers, or 2 nucleotide modifiers aresubstituted for the ribonucleotides on the 3′ end of the sense strand.When sterically hindered molecules are utilized, they are attached tothe ribonucleotide at the 3′ end of the antisense strand. Thus, thelength of the strand does not change with the incorporation of themodifiers. In another embodiment, the invention contemplatessubstituting two DNA bases in the dsRNA to direct the orientation ofDicer processing. In a further invention, two terminal DNA bases arelocated on the 3′ end of the sense strand in place of tworibonucleotides forming a blunt end of the duplex on the 5′ end of theantisense strand and the 3′ end of the sense strand, and atwo-nucleotide RNA overhang is located on the 3′-end of the antisensestrand. This is an asymmetric composition with DNA on the blunt end andRNA bases on the overhanging end.

In certain other embodiments, the antisense strand of a DsiRNA agent ismodified for Dicer processing by suitable modifiers located at the 3′end of the antisense strand, i.e., the DsiRNA agent is designed todirect orientation of Dicer binding and processing. Suitable modifiersinclude nucleotides such as deoxyribonucleotides,dideoxyribonucleotides, acyclonucleotides and the like and stericallyhindered molecules, such as fluorescent molecules and the like.Acyclonucleotides substitute a 2-hydroxyethoxymethyl group for the2′-deoxyribofuranosyl sugar normally present in dNMPs. Other nucleotidemodifiers could include 3′-deoxyadenosine (cordycepin),3′-azido-3′-deoxythymidine (AZT), 2′,3′-dideoxyinosine (ddI),2′,3′-dideoxy-3′-thiacytidine (3TC),2′,3′-didehydro-2′,3′-dideoxythymidine (d4T) and the monophosphatenucleotides of 3′-azido-3′-deoxythymidine (AZT),2′,3′-dideoxy-3′-thiacytidine (3TC) and2′,3′-didehydro-2′,3′-dideoxythymidine (d4T). In one embodiment,deoxynucleotides are used as the modifiers. When nucleotide modifiersare utilized, 1-3 nucleotide modifiers, or 2 nucleotide modifiers aresubstituted for the ribonucleotides on the 3′ end of the antisensestrand. When sterically hindered molecules are utilized, they areattached to the ribonucleotide at the 3′ end of the antisense strand.Thus, the length of the strand does not change with the incorporation ofthe modifiers. In another embodiment, the invention contemplatessubstituting two DNA bases in the dsRNA to direct the orientation ofDicer processing. In a further invention, two terminal DNA bases arelocated on the 3′ end of the antisense strand in place of tworibonucleotides forming a blunt end of the duplex on the 5′ end of thesense strand and the 3′ end of the antisense strand, and atwo-nucleotide RNA overhang is located on the 3′-end of the sensestrand. This is also an asymmetric composition with DNA on the blunt endand RNA bases on the overhanging end.

The sense and antisense strands anneal under biological conditions, suchas the conditions found in the cytoplasm of a cell. In addition, aregion of one of the sequences, particularly of the antisense strand, ofthe dsRNA has a sequence length of at least 19 nucleotides, whereinthese nucleotides are adjacent to the 3′ end of antisense strand and aresufficiently complementary to a nucleotide sequence of the target MYCRNA.

Additionally, the DsiRNA agent structure can be optimized to ensure thatthe oligonucleotide segment generated from Dicer's cleavage will be theportion of the oligonucleotide that is most effective in inhibiting geneexpression. For example, in one embodiment of the invention, a 27-bpoligonucleotide of the DsiRNA agent structure is synthesized wherein theanticipated 21 to 22-bp segment that will inhibit gene expression islocated on the 3′-end of the antisense strand. The remaining baseslocated on the 5′-end of the antisense strand will be cleaved by Dicerand will be discarded. This cleaved portion can be homologous (i.e.,based on the sequence of the target sequence) or non-homologous andadded to extend the nucleic acid strand.

US 2007/0265220 discloses that 27mer DsiRNAs showed improved stabilityin serum over comparable 21mer siRNA compositions, even absent chemicalmodification. Modifications of DsiRNA agents, such as inclusion of2′-O-methyl RNA in the antisense strand, in patterns such as detailedabove, when coupled with addition of a 5′ Phosphate, can improvestability of DsiRNA agents. Addition of 5′-phosphate to all strands insynthetic RNA duplexes may be an inexpensive and physiological method toconfer some limited degree of nuclease stability.

The chemical modification patterns of the dsRNA agents of the instantinvention are designed to enhance the efficacy of such agents.Accordingly, such modifications are designed to avoid reducing potencyof dsRNA agents; to avoid interfering with Dicer processing of DsiRNAagents; to improve stability in biological fluids (reduce nucleasesensitivity) of dsRNA agents; or to block or evade detection by theinnate immune system. Such modifications are also designed to avoidbeing toxic and to avoid increasing the cost or impact the ease ofmanufacturing the instant dsRNA agents of the invention.

In certain embodiments of the present invention, an anti-MYC DsiRNAagent has one or more of the following properties: (i) the DsiRNA agentis asymmetric, e.g., has a 3′ overhang on the antisense strand and (ii)the DsiRNA agent has a modified 3′ end on the sense strand to directorientation of Dicer binding and processing of the dsRNA to an activesiRNA. According to this embodiment, the longest strand in the dsRNAcomprises 25-35 nucleotides (e.g., 25, 26, 27, 28, 29, 30, 31, 32, 33,34 or 35 nucleotides). In certain such embodiments, the DsiRNA agent isasymmetric such that the sense strand comprises 25-34 nucleotides andthe 3′ end of the sense strand forms a blunt end with the 5′ end of theantisense strand while the antisense strand comprises 26-35 nucleotidesand forms an overhang on the 3′ end of the antisense strand. In oneembodiment, the DsiRNA agent is asymmetric such that the sense strandcomprises 25-28 nucleotides and the antisense strand comprises 25-30nucleotides. Thus, the resulting dsRNA has an overhang on the 3′ end ofthe antisense strand. The overhang is 1-4 nucleotides, for example 2nucleotides. The sense strand may also have a 5′ phosphate.

The DsiRNA agent can also have one or more of the following additionalproperties: (a) the antisense strand has a right shift from the typical21mer (e.g., the DsiRNA comprises a length of antisense strandnucleotides that extends to the 5′ of a projected Dicer cleavage sitewithin the DsiRNA, with such antisense strand nucleotides base pairedwith corresponding nucleotides of the sense strand extending 3′ of aprojected Dicer cleavage site in the sense strand), (b) the strands maynot be completely complementary, i.e., the strands may contain simplemismatched base pairs (in certain embodiments, the DsiRNAs of theinvention possess 1, 2, 3, 4 or even 5 or more mismatched base pairs,provided that MYC inhibitory activity of the DsiRNA possessingmismatched base pairs is retained at sufficient levels (e.g., retains atleast 50% MYC inhibitory activity or more, at least 60% MYC inhibitoryactivity or more, at least 70% MYC inhibitory activity or more, at least80% MYC inhibitory activity or more, at least 90% MYC inhibitoryactivity or more or at least 95% MYC inhibitory activity or more ascompared to a corresponding DsiRNA not possessing mismatched base pairs.In certain embodiments, mismatched base pairs exist between theantisense and sense strands of a DsiRNA. In some embodiments, mismatchedbase pairs exist (or are predicted to exist) between the antisensestrand and the target RNA. In certain embodiments, the presence of amismatched base pair(s) between an antisense strand residue and acorresponding residue within the target RNA that is located 3′ in thetarget RNA sequence of a projected Ago2 cleavage site retains and mayeven enhance MYC inhibitory activity of a DsiRNA of the invention) and(c) base modifications such as locked nucleic acid(s) may be included inthe 5′ end of the sense strand. A “typical” 21mer siRNA is designedusing conventional techniques. In one technique, a variety of sites arecommonly tested in parallel or pools containing several distinct siRNAduplexes specific to the same target with the hope that one of thereagents will be effective (Ji et al., 2003, FEBS Lett 552: 247-252).Other techniques use design rules and algorithms to increase thelikelihood of obtaining active RNAi effector molecules (Schwarz et al.,2003, Cell 115: 199-208; Khvorova et al., 2003, Cell 115: 209-216;Ui-Tei et al., 2004, Nucleic Acids Res 32: 936-948; Reynolds et al.,2004, Nat Biotechnol 22: 326-330; Krol et al., 2004, J Biol Chem 279:42230-42239; Yuan et al., 2004, Nucl Acids Res 32 (Webserverissue):W130-134; Boese et al., 2005, Methods Enzymol 392: 73-96). Highthroughput selection of siRNA has also been developed (U.S. publishedpatent application No. 2005/0042641 A1). Potential target sites can alsobe analyzed by secondary structure predictions (Heale et al., 2005,Nucleic Acids Res 33(3): e30). This 21mer is then used to design a rightshift to include 3-9 additional nucleotides on the 5′ end of the 21mer.The sequence of these additional nucleotides is not restricted. In oneembodiment, the added ribonucleotides are based on the sequence of thetarget gene. Even in this embodiment, full complementarity between thetarget sequence and the antisense siRNA is not required.

The first and second oligonucleotides of a DsiRNA agent of the instantinvention are not required to be completely complementary. They onlyneed to be sufficiently complementary to anneal under biologicalconditions and to provide a substrate for Dicer that produces a siRNAsufficiently complementary to the target sequence. Locked nucleic acids,or LNA's, are well known to a skilled artisan (Elmen et al., 2005,Nucleic Acids Res 33: 439-447; Kurreck et al., 2002, Nucleic Acids Res30: 1911-1918; Crinelli et al., 2002, Nucleic Acids Res 30: 2435-2443;Braasch and Corey, 2001, Chem Biol 8: 1-7; Bondensgaard et al., 2000,Chemistry 6: 2687-2695; Wahlestedt et al., 2000, Proc Natl Acad Sci USA97: 5633-5638). In one embodiment, an LNA is incorporated at the 5′terminus of the sense strand. In another embodiment, an LNA isincorporated at the 5′ terminus of the sense strand in duplexes designedto include a 3′ overhang on the antisense strand.

In certain embodiments, the DsiRNA agent of the instant invention has anasymmetric structure, with the sense strand having a 25-base pairlength, and the antisense strand having a 27-base pair length with a 2base 3′-overhang. In other embodiments, this DsiRNA agent having anasymmetric structure further contains 2 deoxynucleotides at the 3′ endof the sense strand in place of two of the ribonucleotides.

Certain DsiRNA agent compositions containing two separateoligonucleotides can be linked by a third structure. The third structurewill not block Dicer activity on the DsiRNA agent and will not interferewith the directed destruction of the RNA transcribed from the targetgene. In one embodiment, the third structure may be a chemical linkinggroup. Many suitable chemical linking groups are known in the art andcan be used. Alternatively, the third structure may be anoligonucleotide that links the two oligonucleotides of the DsiRNA agentin a manner such that a hairpin structure is produced upon annealing ofthe two oligonucleotides making up the dsRNA composition. The hairpinstructure will not block Dicer activity on the DsiRNA agent and will notinterfere with the directed destruction of the MYC RNA.

MYC cDNA and Polypeptide Sequences

Known human and mouse MYC cDNA and polypeptide sequences include thefollowing: human MYC NM_002467.4 and corresponding human MYC polypeptidesequence GenBank Accession No. NP_002458.2; and mouse wild-type MYCsequence GenBank Accession No. NM_010849.4 (Mus musculus C57BL/6 MYCtranscript, variant 1) and corresponding mouse MYC polypeptide sequenceGenBank Accession No. NP_034979.3.

In Vitro Assay to Assess dsRNA MYC Inhibitory Activity

An in vitro assay that recapitulates RNAi in a cell-free system can beused to evaluate dsRNA constructs targeting MYC RNA sequence(s), andthus to assess MYC-specific gene inhibitory activity (also referred toherein as MYC inhibitory activity) of a dsRNA. The assay comprises thesystem described by Tuschl et al., 1999, Genes and Development, 13,3191-3197 and Zamore et al., 2000, Cell, 101, 25-33 adapted for use withdsRNA (e.g., DsiRNA) agents directed against MYC RNA. A Drosophilaextract derived from syncytial blastoderm is used to reconstitute RNAiactivity in vitro. Target RNA is generated via in vitro transcriptionfrom a selected MYC expressing plasmid using T7 RNA polymerase or viachemical synthesis. Sense and antisense dsRNA strands (for example, 20uM each) are annealed by incubation in buffer (such as 100 mM potassiumacetate, 30 mM HEPES-KOH, pH 7.4, 2 mM magnesium acetate) for 1 minuteat 90° C. followed by 1 hour at 37° C., then diluted in lysis buffer(for example 100 mM potassium acetate, 30 mM HEPES-KOH at pH 7.4, 2 mMmagnesium acetate). Annealing can be monitored by gel electrophoresis onan agarose gel in TBE buffer and stained with ethidium bromide. TheDrosophila lysate is prepared using zero to two-hour-old embryos fromOregon R flies collected on yeasted molasses agar that are dechorionatedand lysed. The lysate is centrifuged and the supernatant isolated. Theassay comprises a reaction mixture containing 50% lysate [vol/vol], RNA(10-50 pM final concentration), and 10% [vol/vol] lysis buffercontaining dsRNA (10 nM final concentration). The reaction mixture alsocontains 10 mM creatine phosphate, 10 ug/ml creatine phosphokinase, 100um GTP, 100 uM UTP, 100 uM CTP, 500 uM ATP, 5 mM DTT, 0.1 U/uL RNasin(Promega), and 100 uM of each amino acid. The final concentration ofpotassium acetate is adjusted to 100 mM. The reactions are pre-assembledon ice and preincubated at 25° C. for 10 minutes before adding RNA, thenincubated at 25° C. for an additional 60 minutes. Reactions are quenchedwith 4 volumes of 1.25×Passive Lysis Buffer (Promega). Target RNAcleavage is assayed by RT-PCR analysis or other methods known in the artand are compared to control reactions in which dsRNA is omitted from thereaction.

Alternately, internally-labeled target RNA for the assay is prepared byin vitro transcription in the presence of [α-³²P] CTP, passed over a G50Sephadex column by spin chromatography and used as target RNA withoutfurther purification. Optionally, target RNA is 5′-³²P-end labeled usingT4 polynucleotide kinase enzyme. Assays are performed as described aboveand target RNA and the specific RNA cleavage products generated by RNAiare visualized on an autoradiograph of a gel. The percentage of cleavageis determined by PHOSPHOR IMAGER® (autoradiography) quantitation ofbands representing intact control RNA or RNA from control reactionswithout dsRNA and the cleavage products generated by the assay.

In one embodiment, this assay is used to determine target sites in theMYC RNA target for dsRNA mediated RNAi cleavage, wherein a plurality ofdsRNA constructs are screened for RNAi mediated cleavage of the MYC RNAtarget, for example, by analyzing the assay reaction by electrophoresisof labeled target RNA, or by northern blotting, as well as by othermethodology well known in the art.

In certain embodiments, a dsRNA of the invention is deemed to possessMYC inhibitory activity if, e.g., a 50% reduction in MYC RNA levels isobserved in a system, cell, tissue or organism, relative to a suitablecontrol. Additional metes and bounds for determination of MYC inhibitoryactivity of a dsRNA of the invention are described supra.

Conjugation and Delivery of Anti-MYC dsRNA Agents

In certain embodiments the present invention relates to a method fortreating a subject having a MYC-associated disease or disorder, or atrisk of developing a MYC-associated disease or disorder. In suchembodiments, the dsRNA can act as novel therapeutic agents forcontrolling the MYC-associated disease or disorder. The method comprisesadministering a pharmaceutical composition of the invention to thepatient (e.g., human), such that the expression, level and/or activityof a MYC RNA is reduced. The expression, level and/or activity of apolypeptide encoded by a MYC RNA might also be reduced by a dsRNA of theinstant invention, even where said dsRNA is directed against anon-coding region of the MYC transcript (e.g., a targeted 5′ UTR or 3′UTR sequence). Because of their high specificity, the dsRNAs of thepresent invention can specifically target MYC sequences of cells andtissues, optionally in an allele-specific manner where polymorphicalleles exist within an individual and/or population.

In the treatment of a MYC-associated disease or disorder, the dsRNA canbe brought into contact with the cells or tissue of a subject, e.g., thecells or tissue of a subject exhibiting disregulation of MYC and/orotherwise targeted for reduction of MYC levels. For example, dsRNAsubstantially identical to all or part of a MYC RNA sequence, may bebrought into contact with or introduced into such a cell, either in vivoor in vitro. Similarly, dsRNA substantially identical to all or part ofa MYC RNA sequence may administered directly to a subject having or atrisk of developing a MYC-associated disease or disorder.

Therapeutic use of the dsRNA agents of the instant invention can involveuse of formulations of dsRNA agents comprising multiple different dsRNAagent sequences. For example, two or more, three or more, four or more,five or more, etc. of the presently described agents can be combined toproduce a formulation that, e.g., targets multiple different regions ofthe MYC RNA, or that not only target MYC RNA but also target, e.g.,cellular target genes associated with a MYC-associated disease ordisorder. A dsRNA agent of the instant invention may also be constructedsuch that either strand of the dsRNA agent independently targets two ormore regions of MYC RNA, or such that one of the strands of the dsRNAagent targets a cellular target gene of MYC known in the art.

Use of multifunctional dsRNA molecules that target more then one regionof a target nucleic acid molecule can also provide potent inhibition ofMYC RNA levels and expression. For example, a single multifunctionaldsRNA construct of the invention can target both the MYC-1916 andMYC-1572 sites simultaneously; additionally and/or alternatively, singleor multifunctional agents of the invention can be designed toselectively target one splice variant of MYC over another.

Thus, the dsRNA agents of the instant invention, individually, or incombination or in conjunction with other drugs, can be used to treat,inhibit, reduce, or prevent a MYC-associated disease or disorder. Forexample, the dsRNA molecules can be administered to a subject or can beadministered to other appropriate cells evident to those skilled in theart, individually or in combination with one or more drugs underconditions suitable for the treatment.

The dsRNA molecules also can be used in combination with other knowntreatments to treat, inhibit, reduce, or prevent a MYC-associateddisease or disorder in a subject or organism. For example, the describedmolecules could be used in combination with one or more known compounds,treatments, or procedures to treat, inhibit, reduce, or prevent aMYC-associated disease or disorder in a subject or organism as are knownin the art.

A dsRNA agent of the invention can be conjugated (e.g., at its 5′ or 3′terminus of its sense or antisense strand) or unconjugated to anothermoiety (e.g. a non-nucleic acid moiety such as a peptide), an organiccompound (e.g., a dye, cholesterol, or the like). Modifying dsRNA agentsin this way may improve cellular uptake or enhance cellular targetingactivities of the resulting dsRNA agent derivative as compared to thecorresponding unconjugated dsRNA agent, are useful for tracing the dsRNAagent derivative in the cell, or improve the stability of the dsRNAagent derivative compared to the corresponding unconjugated dsRNA agent.

Methods of Introducing Nucleic Acids, Vectors, and Host Cells

dsRNA agents of the invention may be directly introduced into a cell(i.e., intracellularly); or introduced extracellularly into a cavity,interstitial space, into the circulation of an organism, introducedorally, or may be introduced by bathing a cell or organism in a solutioncontaining the nucleic acid. Vascular or extravascular circulation, theblood or lymph system, and the cerebrospinal fluid are sites where thenucleic acid may be introduced.

The dsRNA agents of the invention can be introduced using nucleic aciddelivery methods known in art including injection of a solutioncontaining the nucleic acid, bombardment by particles covered by thenucleic acid, soaking the cell or organism in a solution of the nucleicacid, or electroporation of cell membranes in the presence of thenucleic acid. Other methods known in the art for introducing nucleicacids to cells may be used, such as lipid-mediated carrier transport,chemical-mediated transport, and cationic liposome transfection such ascalcium phosphate, and the like. The nucleic acid may be introducedalong with other components that perform one or more of the followingactivities: enhance nucleic acid uptake by the cell or other-wiseincrease inhibition of the target MYC RNA.

A cell having a target MYC RNA may be from the germ line or somatic,totipotent or pluripotent, dividing or non-dividing, parenchyma orepithelium, immortalized or transformed, or the like. The cell may be astem cell or a differentiated cell. Cell types that are differentiatedinclude adipocytes, fibroblasts, myocytes, cardiomyocytes, endothelium,neurons, glia, blood cells, megakaryocytes, lymphocytes, macrophages,neutrophils, eosinophils, basophils, mast cells, leukocytes,granulocytes, keratinocytes, chondrocytes, osteoblasts, osteoclasts,hepatocytes, and cells of the endocrine or exocrine glands.

Depending on the particular target MYC RNA sequence and the dose ofdsRNA agent material delivered, this process may provide partial orcomplete loss of function for the MYC RNA. A reduction or loss of RNAlevels or expression (either MYC RNA expression or encoded polypeptideexpression) in at least 50%, 60%, 70%, 80%, 90%, 95% or 99% or more oftargeted cells is exemplary Inhibition of MYC RNA levels or expressionrefers to the absence (or observable decrease) in the level of MYC RNAor MYC RNA-encoded protein. Specificity refers to the ability to inhibitthe MYC RNA without manifest effects on other genes of the cell. Theconsequences of inhibition can be confirmed by examination of theoutward properties of the cell or organism or by biochemical techniquessuch as RNA solution hybridization, nuclease protection, Northernhybridization, reverse transcription, gene expression monitoring with amicroarray, antibody binding, enzyme linked immunosorbent assay (ELISA),Western blotting, radioimmunoassay (RIA), other immunoassays, andfluorescence activated cell analysis (FACS) Inhibition of target MYC RNAsequence(s) by the dsRNA agents of the invention also can be measuredbased upon the effect of administration of such dsRNA agents upondevelopment/progression of a MYC-associated disease or disorder, e.g.,tumor formation, growth, metastasis, etc., either in vivo or in vitro.Treatment and/or reductions in tumor or cancer cell levels can includehalting or reduction of growth of tumor or cancer cell levels orreductions of, e.g., 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or99% or more, and can also be measured in logarithmic terms, e.g.,10-fold, 100-fold, 1000-fold, 10⁵-fold, 10⁶-fold, 10⁷-fold reduction incancer cell levels could be achieved via administration of the dsRNAagents of the invention to cells, a tissue, or a subject.

For RNA-mediated inhibition in a cell line or whole organism, expressiona reporter or drug resistance gene whose protein product is easilyassayed can be measured. Such reporter genes include acetohydroxyacidsynthase (AHAS), alkaline phosphatase (AP), beta galactosidase (LacZ),beta glucoronidase (GUS), chloramphenicol acetyltransferase (CAT), greenfluorescent protein (GFP), horseradish peroxidase (HRP), luciferase(Luc), nopaline synthase (NOS), octopine synthase (OCS), and derivativesthereof. Multiple selectable markers are available that conferresistance to ampicillin, bleomycin, chloramphenicol, gentamycin,hygromycin, kanamycin, lincomycin, methotrexate, phosphinothricin,puromycin, and tetracyclin. Depending on the assay, quantitation of theamount of gene expression allows one to determine a degree of inhibitionwhich is greater than 10%, 33%, 50%, 90%, 95% or 99% as compared to acell not treated according to the present invention.

Lower doses of injected material and longer times after administrationof RNA silencing agent may result in inhibition in a smaller fraction ofcells (e.g., at least 10%, 20%, 50%, 75%, 90%, or 95% of targetedcells). Quantitation of gene expression in a cell may show similaramounts of inhibition at the level of accumulation of target MYC RNA ortranslation of target protein. As an example, the efficiency ofinhibition may be determined by assessing the amount of gene product inthe cell; RNA may be detected with a hybridization probe having anucleotide sequence outside the region used for the inhibitory dsRNA, ortranslated polypeptide may be detected with an antibody raised againstthe polypeptide sequence of that region.

The dsRNA agent may be introduced in an amount which allows delivery ofat least one copy per cell. Higher doses (e.g., at least 5, 10, 100, 500or 1000 copies per cell) of material may yield more effectiveinhibition; lower doses may also be useful for specific applications.

MYC Biology and MYC-Targeting Therapeutics

MYC (c-MYC) is a proto-oncogene, which is overexpressed in a wide rangeof human cancers. When it is specifically mutated, or overexpressed, itincreases cell proliferation and functions as an oncogene. The MYC geneencodes for a transcription factor that regulates expression of 15% ofall genes through binding on Enhancer Box sequences (E-boxes) andrecruiting histone acetyltransferases (HATs). MYC belongs to the MYCfamily of transcription factors, which also includes N-MYC and L-MYCgenes. MYC-family transcription factors contain a bHLH/LZ (basicHelix-Loop-Helix Leucine Zipper) domain. Myc protein, through its bHLHdomain, can bind to DNA, while the leucine zipper domain of Myc allowsfor dimerization with a partner protein, Max, another bHLH transcriptionfactor.

The MYC gene was initially identified and characterized in Burkitt'slymphoma patients. In Burkitt's lymphoma, cancer cells show chromosomaltranslocations, frequently involving Chromosome 8. Cloning of the fusionchromosome break point revealed a gene that was similar tomyelocytomatosis viral oncogene (v-MYC). Thus, the newfound cellulargene was named c-MYC.

Myc protein is a transcription factor that activates expression of agreat number of genes through binding on consensus sequences (EnhancerBox sequences (E-boxes)) and recruiting histone acetyltransferases(HATs). It can also act as a transcriptional repressor. By binding Miz-1transcription factor and displacing the p300 co-activator, it inhibitsexpression of Miz-1 target genes.

Myc is activated through various mitogenic signaling pathways, such asWnt, Shh and EGF (via the MAPK/ERK pathway). By modifying the expressionof its target genes, Myc activation results in numerous biologicaleffects, including enhancement of cell proliferation (upregulatescyclins, downregulates p21), regulation of cell growth (upregulatesribosomal RNA and proteins), apoptosis (upregulates Bcl-2),differentiation and stem cell self-renewal. MYC is a strongproto-oncogene and it has been found to be upregulated in many types ofcancers.

During discovery of MYC, chromosomes that translocated to Chromosome 8were identified to contain immunoglobulin (Ig) genes at the break point.Post-translocation, enhancers of immunoglobin genes were instead causingoverexpression of MYC in lymphoma cells. Transgenic mouse models thatoverexpress MYC were then developed to study the mechanism oftumorigenesis in Burkitt's lymphoma—e.g., transgenic mice overexpressingMYC (MYC under control of the IgM heavy chain enhancer) developedlymphomas when MYC was placed under control of the IgM heavy chainenhancer, or various other types of tumor when MYC overexpressionoccurred in other tissues (e.g., liver, breast), illustrating thepotency of MYC as an oncogene.

References useful for understanding c-MYC biology include: Gearhart J,Pashos E E, Prasad M K, Pluripotency Redeux—advances in stem-cellresearcg, N Engl J Med 357(15):1469. Ruf I K, Rhyne P W, Yang H, et al.(2002). “EBV regulates c-MYC, apoptosis, and tumorigenicity in Burkitt'slymphoma,” Curr. Top. Microbiol. Immunol. 258: 153-60. PMID 11443860.Lüscher B (2001). “Function and regulation of the transcription factorsof the Myc/Max/Mad network,”. Gene 277 (1-2): 1-14. PMID 11602341.Hoffman B, Amanullah A, Shafarenko M, Liebermann D A (2002), “Theproto-oncogene c-myc in hematopoietic development and leukemogenesis,”Oncogene 21 (21): 3414-21, doi:10.1038/sj.one.1205400. PMID 12032779.Pelengaris S, Khan M, Evan G (2002), “c-MYC: more than just a matter oflife and death,” Nat. Rev. Cancer 2 (10): 764-76, doi:10.1038/nrc904.PMID 12360279. Nilsson J A, Cleveland J L (2004), “Myc pathwaysprovoking cell suicide and cancer,” Oncogene 22 (56): 9007-21.doi:10.1038/sj.one.1207261. PMID 14663479. Dang C V, O'donnell K A,Juopperi T (2005), “The great MYC escape in tumorigenesis,” Cancer Cell8 (3): 177-8, doi:10.1016/j.ccr.2005.08.005. PMID 16169462. Dang C V, LiF, Lee L A (2007), “Could MYC induction of mitochondrial biogenesis belinked to ROS production and genomic instability?” Cell Cycle 4 (11):1465-6, PMID 16205115. Coller H A, Forman J J, Legesse-Miller A (2007),“‘Myc’ed messages′: myc induces transcription of E2F1 while inhibitingits translation via a microRNA polycistron,” PLoS Genet. 3(8): e146,doi:10.1371/journal.pgen.0030146. PMID 17784791. Astrin S M, Laurence J(1992), “Human immunodeficiency virus activates c-myc and Epstein-Barrvirus in human B lymphocytes,” Ann. N.Y. Acad. Sci. 651: 422-32, PMID1318011. Bernstein P L, Herrick D J, Prokipcak R D, Ross J (1992),“Control of c-myc mRNA half-life in vitro by a protein capable ofbinding to a coding region stability determinant,” Genes Dev. 6 (4):642-54, PMID 1559612. lijima S, Teraoka H, Date T, Tsukada K (1992),“DNA-activated protein kinase in Raji Burkitt's lymphoma cells.Phosphorylation of c-Myc oncoprotein,” Eur. J. Biochem. 206 (2):595-603, PMID 1597196. Seth A, Alvarez E, Gupta S, Davis R J (1992), “Aphosphorylation site located in the NH2-terminal domain of c-Mycincreases transactivation of gene expression,” J. Biol. Chem. 266 (35):23521-4, PMID 1748630. Takahashi E, Hori T, O'Connell P, et al. (1991),“Mapping of the MYC gene to band 8q24.12-q24.13 by R-banding and distalto fra(8)(q24.11), FRA8E, by fluorescence in situ hybridization,”Cytogenet. Cell Genet. 57 (2-3): 109-11, PMID 1914517. Blackwood E M,Eisenman R N (1991), “Max: a helix-loop-helix zipper protein that formsa sequence-specific DNA-binding complex with Myc,” Science 251 (4998):1211-7, PMID 2006410. Gazin C, Rigolet M, Briand J P, et al. (1986),“Immunochemical detection of proteins related to the human c-myc exon1,” EMBO J. 5 (9): 2241-50, PMID 2430795. Lüscher B, Kuenzel E A, KrebsE G, Eisenman R N (1989), “Myc oncoproteins are phosphorylated by caseinkinase II,” EMBO J. 8 (4): 1111-9, PMID 2663470. Finver S N, NishikuraK, Finger L R, et al. (1988), “Sequence analysis of the MYC oncogeneinvolved in the t(8; 14)(q24;q11) chromosome translocation in a humanleukemia T-cell line indicates that putative regulatory regions are notaltered,” Proc. Natl. Acad. Sci. U.S.A. 85 (9): 3052-6, PMID 2834731.Showe L C, Moore R C, Erikson J, Croce C M (1987), “MYC oncogeneinvolved in a t(8; 22) chromosome translocation is not altered in itsputative regulatory regions,” Proc. Natl. Acad. Sci. U.S.A. 84 (9):2824-8, PMID 3033665. Guilhot S, Petridou B, Syed-Hussain S, Galibert F(1989), “Nucleotide sequence 3′ to the human c-myc oncogene; presence ofa long inverted repeat,” Gene 72 (1-2): 105-8, PMID 3243428. Hann S R,King M W, Bentley D L, et al. (1988), “A non-AUG translationalinitiation in c-myc exon 1 generates an N-terminally distinct proteinwhose synthesis is disrupted in Burkitt's lymphomas,” Cell 52 (2):185-95; PMID 3277717.

MYC-inhibiting small molecules have recently been identified (Moyer.Nature Medicine 17: 1325). The MYC-inhibiting double stranded nucleicacids of the instant invention can be used alone, or in combination withany art-recognized MYC-targeting therapeutic, such as those recitedtherein.

Pharmaceutical Compositions

In certain embodiments, the present invention provides for apharmaceutical composition comprising the dsRNA agent of the presentinvention. The dsRNA agent sample can be suitably formulated andintroduced into the environment of the cell by any means that allows fora sufficient portion of the sample to enter the cell to induce genesilencing, if it is to occur. Many formulations for dsRNA are known inthe art and can be used so long as the dsRNA gains entry to the targetcells so that it can act. See, e.g., U.S. published patent applicationNos. 2004/0203145 A1 and 2005/0054598 A1. For example, the dsRNA agentof the instant invention can be formulated in buffer solutions such asphosphate buffered saline solutions, liposomes, micellar structures, andcapsids. Formulations of dsRNA agent with cationic lipids can be used tofacilitate transfection of the dsRNA agent into cells. For example,cationic lipids, such as lipofectin (U.S. Pat. No. 5,705,188), cationicglycerol derivatives, and polycationic molecules, such as polylysine(published PCT International Application WO 97/30731), can be used.Suitable lipids include Oligofectamine, Lipofectamine (LifeTechnologies), NC388 (Ribozyme Pharmaceuticals, Inc., Boulder, Colo.),or FuGene 6 (Roche) all of which can be used according to themanufacturer's instructions.

Such compositions typically include the nucleic acid molecule and apharmaceutically acceptable carrier. As used herein the language“pharmaceutically acceptable carrier” includes saline, solvents,dispersion media, coatings, antibacterial and antifungal agents,isotonic and absorption delaying agents, and the like, compatible withpharmaceutical administration. Supplementary active compounds can alsobe incorporated into the compositions.

A pharmaceutical composition is formulated to be compatible with itsintended route of administration. Examples of routes of administrationinclude parenteral, e.g., intravenous, intradermal, subcutaneous, oral(e.g., inhalation), transdermal (topical), transmucosal, and rectaladministration. Solutions or suspensions used for parenteral,intradermal, or subcutaneous application can include the followingcomponents: a sterile diluent such as water for injection, salinesolution, fixed oils, polyethylene glycols, glycerine, propylene glycolor other synthetic solvents; antibacterial agents such as benzyl alcoholor methyl parabens; antioxidants such as ascorbic acid or sodiumbisulfite; chelating agents such as ethylenediaminetetraacetic acid;buffers such as acetates, citrates or phosphates and agents for theadjustment of tonicity such as sodium chloride or dextrose. pH can beadjusted with acids or bases, such as hydrochloric acid or sodiumhydroxide. The parenteral preparation can be enclosed in ampoules,disposable syringes or multiple dose vials made of glass or plastic.

Pharmaceutical compositions suitable for injectable use include sterileaqueous solutions (where water soluble) or dispersions and sterilepowders for the extemporaneous preparation of sterile injectablesolutions or dispersion. For intravenous administration, suitablecarriers include physiological saline, bacteriostatic water, CremophorEL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In allcases, the composition must be sterile and should be fluid to the extentthat easy syringability exists. It should be stable under the conditionsof manufacture and storage and must be preserved against thecontaminating action of microorganisms such as bacteria and fungi. Thecarrier can be a solvent or dispersion medium containing, for example,water, ethanol, polyol (for example, glycerol, propylene glycol, andliquid polyetheylene glycol, and the like), and suitable mixturesthereof. The proper fluidity can be maintained, for example, by the useof a coating such as lecithin, by the maintenance of the requiredparticle size in the case of dispersion and by the use of surfactants.Prevention of the action of microorganisms can be achieved by variousantibacterial and antifungal agents, for example, parabens,chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In manycases, it will be preferable to include isotonic agents, for example,sugars, polyalcohols such as manitol, sorbitol, sodium chloride in thecomposition. Prolonged absorption of the injectable compositions can bebrought about by including in the composition an agent which delaysabsorption, for example, aluminum monostearate and gelatin.

Sterile injectable solutions can be prepared by incorporating the activecompound in the required amount in a selected solvent with one or acombination of ingredients enumerated above, as required, followed byfiltered sterilization. Generally, dispersions are prepared byincorporating the active compound into a sterile vehicle, which containsa basic dispersion medium and the required other ingredients from thoseenumerated above. In the case of sterile powders for the preparation ofsterile injectable solutions, the preferred methods of preparation arevacuum drying and freeze-drying which yields a powder of the activeingredient plus any additional desired ingredient from a previouslysterile-filtered solution thereof.

Oral compositions generally include an inert diluent or an ediblecarrier. For the purpose of oral therapeutic administration, the activecompound can be incorporated with excipients and used in the form oftablets, troches, or capsules, e.g., gelatin capsules. Oral compositionscan also be prepared using a fluid carrier for use as a mouthwash.Pharmaceutically compatible binding agents, and/or adjuvant materialscan be included as part of the composition. The tablets, pills,capsules, troches and the like can contain any of the followingingredients, or compounds of a similar nature: a binder such asmicrocrystalline cellulose, gum tragacanth or gelatin; an excipient suchas starch or lactose, a disintegrating agent such as alginic acid,Primogel, or corn starch; a lubricant such as magnesium stearate orSterotes; a glidant such as colloidal silicon dioxide; a sweeteningagent such as sucrose or saccharin; or a flavoring agent such aspeppermint, methyl salicylate, or orange flavoring.

For administration by inhalation, the compounds are delivered in theform of an aerosol spray from pressured container or dispenser whichcontains a suitable propellant, e.g., a gas such as carbon dioxide, or anebulizer. Such methods include those described in U.S. Pat. No.6,468,798.

Systemic administration can also be by transmucosal or transdermalmeans. For transmucosal or transdermal administration, penetrantsappropriate to the barrier to be permeated are used in the formulation.Such penetrants are generally known in the art, and include, forexample, for transmucosal administration, detergents, bile salts, andfusidic acid derivatives. Transmucosal administration can beaccomplished through the use of nasal sprays or suppositories. Fortransdermal administration, the active compounds are formulated intoointments, salves, gels, or creams as generally known in the art.

The compounds can also be prepared in the form of suppositories (e.g.,with conventional suppository bases such as cocoa butter and otherglycerides) or retention enemas for rectal delivery.

The compounds can also be administered by transfection or infectionusing methods known in the art, including but not limited to the methodsdescribed in McCaffrey et al. (2002), Nature, 418(6893), 38-9(hydrodynamic transfection); Xia et al. (2002), Nature Biotechnol.,20(10), 1006-10 (viral-mediated delivery); or Putnam (1996), Am. J.Health Syst. Pharm. 53(2), 151-160, erratum at Am. J. Health Syst.Pharm. 53(3), 325 (1996).

The compounds can also be administered by a method suitable foradministration of nucleic acid agents, such as a DNA vaccine. Thesemethods include gene guns, bio injectors, and skin patches as well asneedle-free methods such as the micro-particle DNA vaccine technologydisclosed in U.S. Pat. No. 6,194,389, and the mammalian transdermalneedle-free vaccination with powder-form vaccine as disclosed in U.S.Pat. No. 6,168,587. Additionally, intranasal delivery is possible, asdescribed in, inter alia, Hamajima et al. (1998), Clin. Immunol.Immunopathol., 88(2), 205-10. Liposomes (e.g., as described in U.S. Pat.No. 6,472,375) and microencapsulation can also be used. Biodegradabletargetable microparticle delivery systems can also be used (e.g., asdescribed in U.S. Pat. No. 6,471,996).

In one embodiment, the active compounds are prepared with carriers thatwill protect the compound against rapid elimination from the body, suchas a controlled release formulation, including implants andmicroencapsulated delivery systems. Biodegradable, biocompatiblepolymers can be used, such as ethylene vinyl acetate, polyanhydrides,polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Suchformulations can be prepared using standard techniques. The materialscan also be obtained commercially from Alza Corporation and NovaPharmaceuticals, Inc. Liposomal suspensions (including liposomestargeted to infected cells with monoclonal antibodies to viral antigens)can also be used as pharmaceutically acceptable carriers. These can beprepared according to methods known to those skilled in the art, forexample, as described in U.S. Pat. No. 4,522,811.

Toxicity and therapeutic efficacy of such compounds can be determined bystandard pharmaceutical procedures in cell cultures or experimentalanimals, e.g., for determining the LD₅₀ (the dose lethal to 50% of thepopulation) and the ED₅₀ (the dose therapeutically effective in 50% ofthe population). The dose ratio between toxic and therapeutic effects isthe therapeutic index and it can be expressed as the ratio LD₅₀/ED₅₀.Compounds which exhibit high therapeutic indices are preferred. Whilecompounds that exhibit toxic side effects may be used, care should betaken to design a delivery system that targets such compounds to thesite of affected tissue in order to minimize potential damage touninfected cells and, thereby, reduce side effects.

The data obtained from the cell culture assays and animal studies can beused in formulating a range of dosage for use in humans. The dosage ofsuch compounds lies preferably within a range of circulatingconcentrations that include the ED₅₀ with little or no toxicity. Thedosage may vary within this range depending upon the dosage formemployed and the route of administration utilized. For a compound usedin the method of the invention, the therapeutically effective dose canbe estimated initially from cell culture assays. A dose may beformulated in animal models to achieve a circulating plasmaconcentration range that includes the IC₅₀ (i.e., the concentration ofthe test compound which achieves a half-maximal inhibition of symptoms)as determined in cell culture. Such information can be used to moreaccurately determine useful doses in humans. Levels in plasma may bemeasured, for example, by high performance liquid chromatography.

As defined herein, a therapeutically effective amount of a nucleic acidmolecule (i.e., an effective dosage) depends on the nucleic acidselected. For instance, single dose amounts of a dsRNA (or, e.g., aconstruct(s) encoding for such dsRNA) in the range of approximately 1 pgto 1000 mg may be administered; in some embodiments, 10, 30, 100, or1000 pg, or 10, 30, 100, or 1000 ng, or 10, 30, 100, or 1000 fig, or 10,30, 100, or 1000 mg may be administered. In some embodiments, 1-5 g ofthe compositions can be administered. The compositions can beadministered one from one or more times per day to one or more times perweek; including once every other day. The skilled artisan willappreciate that certain factors may influence the dosage and timingrequired to effectively treat a subject, including but not limited tothe severity of the disease or disorder, previous treatments, thegeneral health and/or age of the subject, and other diseases present.Moreover, treatment of a subject with a therapeutically effective amountof a nucleic acid (e.g., dsRNA), protein, polypeptide, or antibody caninclude a single treatment or, preferably, can include a series oftreatments.

The nucleic acid molecules of the invention can be inserted intoexpression constructs, e.g., viral vectors, retroviral vectors,expression cassettes, or plasmid viral vectors, e.g., using methodsknown in the art, including but not limited to those described in Xia etal., (2002), supra. Expression constructs can be delivered to a subjectby, for example, inhalation, orally, intravenous injection, localadministration (see U.S. Pat. No. 5,328,470) or by stereotacticinjection (see e.g., Chen et al. (1994), Proc. Natl. Acad. Sci. USA, 91,3054-3057). The pharmaceutical preparation of the delivery vector caninclude the vector in an acceptable diluent, or can comprise a slowrelease matrix in which the delivery vehicle is imbedded. Alternatively,where the complete delivery vector can be produced intact fromrecombinant cells, e.g., retroviral vectors, the pharmaceuticalpreparation can include one or more cells which produce the genedelivery system.

The expression constructs may be constructs suitable for use in theappropriate expression system and include, but are not limited toretroviral vectors, linear expression cassettes, plasmids and viral orvirally-derived vectors, as known in the art. Such expression constructsmay include one or more inducible promoters, RNA Pol III promotersystems such as U6 snRNA promoters or H1 RNA polymerase III promoters,or other promoters known in the art. The constructs can include one orboth strands of the siRNA. Expression constructs expressing both strandscan also include loop structures linking both strands, or each strandcan be separately transcribed from separate promoters within the sameconstruct. Each strand can also be transcribed from a separateexpression construct, e.g., Tuschl (2002, Nature Biotechnol 20:500-505).

It can be appreciated that the method of introducing dsRNA agents intothe environment of the cell will depend on the type of cell and the makeup of its environment. For example, when the cells are found within aliquid, one preferable formulation is with a lipid formulation such asin lipofectamine and the dsRNA agents can be added directly to theliquid environment of the cells. Lipid formulations can also beadministered to animals such as by intravenous, intramuscular, orintraperitoneal injection, or orally or by inhalation or other methodsas are known in the art. When the formulation is suitable foradministration into animals such as mammals and more specificallyhumans, the formulation is also pharmaceutically acceptable.Pharmaceutically acceptable formulations for administeringoligonucleotides are known and can be used. In some instances, it may bepreferable to formulate dsRNA agents in a buffer or saline solution anddirectly inject the formulated dsRNA agents into cells, as in studieswith oocytes. The direct injection of dsRNA agent duplexes may also bedone. For suitable methods of introducing dsRNA (e.g., DsiRNA agents),see U.S. published patent application No. 2004/0203145 A1.

Suitable amounts of a dsRNA agent must be introduced and these amountscan be empirically determined using standard methods. Typically,effective concentrations of individual dsRNA agent species in theenvironment of a cell will be 50 nanomolar or less, 10 nanomolar orless, or compositions in which concentrations of 1 nanomolar or less canbe used. In another embodiment, methods utilizing a concentration of 200picomolar or less, 100 picomolar or less, 50 picomolar or less, 20picomolar or less, and even a concentration of 10 picomolar or less, 5picomolar or less, 2 picomolar or less or 1 picomolar or less can beused in many circumstances.

The method can be carried out by addition of the dsRNA agentcompositions to an extracellular matrix in which cells can live providedthat the dsRNA agent composition is formulated so that a sufficientamount of the dsRNA agent can enter the cell to exert its effect. Forexample, the method is amenable for use with cells present in a liquidsuch as a liquid culture or cell growth media, in tissue explants, or inwhole organisms, including animals, such as mammals and especiallyhumans.

The level or activity of a MYC RNA can be determined by a suitablemethod now known in the art or that is later developed. It can beappreciated that the method used to measure a target RNA and/or theexpression of a target RNA can depend upon the nature of the target RNA.For example, where the target MYC RNA sequence encodes a protein, theterm “expression” can refer to a protein or the MYC RNA/transcriptderived from the MYC gene (either genomic or of exogenous origin). Insuch instances the expression of the target MYC RNA can be determined bymeasuring the amount of MYC RNA/transcript directly or by measuring theamount of Myc protein. Protein can be measured in protein assays such asby staining or immunoblotting or, if the protein catalyzes a reactionthat can be measured, by measuring reaction rates. All such methods areknown in the art and can be used. Where target MYC RNA levels are to bemeasured, art-recognized methods for detecting RNA levels can be used(e.g., RT-PCR, Northern Blotting, etc.). In targeting MYC RNAs with thedsRNA agents of the instant invention, it is also anticipated thatmeasurement of the efficacy of a dsRNA agent in reducing levels of MYCRNA or protein in a subject, tissue, in cells, either in vitro or invivo, or in cell extracts can also be used to determine the extent ofreduction of MYC-associated phenotypes (e.g., disease or disorders,e.g., cancer or tumor formation, growth, metastasis, spread, etc.). Theabove measurements can be made on cells, cell extracts, tissues, tissueextracts or other suitable source material.

The determination of whether the expression of a MYC RNA has beenreduced can be by a suitable method that can reliably detect changes inRNA levels. Typically, the determination is made by introducing into theenvironment of a cell undigested dsRNA such that at least a portion ofthat dsRNA agent enters the cytoplasm, and then measuring the level ofthe target RNA. The same measurement is made on identical untreatedcells and the results obtained from each measurement are compared.

The dsRNA agent can be formulated as a pharmaceutical composition whichcomprises a pharmacologically effective amount of a dsRNA agent andpharmaceutically acceptable carrier. A pharmacologically ortherapeutically effective amount refers to that amount of a dsRNA agenteffective to produce the intended pharmacological, therapeutic orpreventive result. The phrases “pharmacologically effective amount” and“therapeutically effective amount” or simply “effective amount” refer tothat amount of an RNA effective to produce the intended pharmacological,therapeutic or preventive result. For example, if a given clinicaltreatment is considered effective when there is at least a 20% reductionin a measurable parameter associated with a disease or disorder, atherapeutically effective amount of a drug for the treatment of thatdisease or disorder is the amount necessary to effect at least a 20%reduction in that parameter.

Suitably formulated pharmaceutical compositions of this invention can beadministered by means known in the art such as by parenteral routes,including intravenous, intramuscular, intraperitoneal, subcutaneous,transdermal, airway (aerosol), rectal, vaginal and topical (includingbuccal and sublingual) administration. In some embodiments, thepharmaceutical compositions are administered by intravenous orintraparenteral infusion or injection.

In general, a suitable dosage unit of dsRNA will be in the range of0.001 to 0.25 milligrams per kilogram body weight of the recipient perday, or in the range of 0.01 to 20 micrograms per kilogram body weightper day, or in the range of 0.001 to 5 micrograms per kilogram of bodyweight per day, or in the range of 1 to 500 nanograms per kilogram ofbody weight per day, or in the range of 0.01 to 10 micrograms perkilogram body weight per day, or in the range of 0.10 to 5 microgramsper kilogram body weight per day, or in the range of 0.1 to 2.5micrograms per kilogram body weight per day. A pharmaceuticalcomposition comprising the dsRNA can be administered once daily.However, the therapeutic agent may also be dosed in dosage unitscontaining two, three, four, five, six or more sub-doses administered atappropriate intervals throughout the day. In that case, the dsRNAcontained in each sub-dose must be correspondingly smaller in order toachieve the total daily dosage unit. The dosage unit can also becompounded for a single dose over several days, e.g., using aconventional sustained release formulation which provides sustained andconsistent release of the dsRNA over a several day period. Sustainedrelease formulations are well known in the art. In this embodiment, thedosage unit contains a corresponding multiple of the daily dose.Regardless of the formulation, the pharmaceutical composition mustcontain dsRNA in a quantity sufficient to inhibit expression of thetarget gene in the animal or human being treated. The composition can becompounded in such a way that the sum of the multiple units of dsRNAtogether contain a sufficient dose.

Data can be obtained from cell culture assays and animal studies toformulate a suitable dosage range for humans. The dosage of compositionsof the invention lies within a range of circulating concentrations thatinclude the ED₅₀ (as determined by known methods) with little or notoxicity. The dosage may vary within this range depending upon thedosage form employed and the route of administration utilized. For acompound used in the method of the invention, the therapeuticallyeffective dose can be estimated initially from cell culture assays. Adose may be formulated in animal models to achieve a circulating plasmaconcentration range of the compound that includes the IC₅₀ (i.e., theconcentration of the test compound which achieves a half-maximalinhibition of symptoms) as determined in cell culture. Such informationcan be used to more accurately determine useful doses in humans. Levelsof dsRNA in plasma may be measured by standard methods, for example, byhigh performance liquid chromatography.

The pharmaceutical compositions can be included in a kit, container,pack, or dispenser together with instructions for administration.

Methods of Treatment

The present invention provides for both prophylactic and therapeuticmethods of treating a subject at risk of (or susceptible to) a diseaseor disorder caused, in whole or in part, by MYC (e.g., misregulationand/or elevation of MYC transcript and/or Myc protein levels), ortreatable via selective targeting of MYC.

“Treatment”, or “treating” as used herein, is defined as the applicationor administration of a therapeutic agent (e.g., a dsRNA agent or vectoror transgene encoding same) to a patient, or application oradministration of a therapeutic agent to an isolated tissue or cell linefrom a patient, who has the disease or disorder, a symptom of disease ordisorder or a predisposition toward a disease or disorder, with thepurpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate,improve or affect the disease or disorder, the symptoms of the diseaseor disorder, or the predisposition toward disease.

In one aspect, the invention provides a method for preventing in asubject, a disease or disorder as described above (including, e.g.,prevention of the commencement of transforming events within a subjectvia inhibition of MYC expression), by administering to the subject atherapeutic agent (e.g., a dsRNA agent or vector or transgene encodingsame). Subjects at risk for the disease can be identified by, forexample, one or a combination of diagnostic or prognostic assays asdescribed herein. Administration of a prophylactic agent can occur priorto the detection of, e.g., cancer in a subject, or the manifestation ofsymptoms characteristic of the disease or disorder, such that thedisease or disorder is prevented or, alternatively, delayed in itsprogression.

Another aspect of the invention pertains to methods of treating subjectstherapeutically, i.e., altering the onset of symptoms of the disease ordisorder. These methods can be performed in vitro (e.g., by culturingthe cell with the dsRNA agent) or, alternatively, in vivo (e.g., byadministering the dsRNA agent to a subject).

With regards to both prophylactic and therapeutic methods of treatment,such treatments may be specifically tailored or modified, based onknowledge obtained from the field of pharmacogenomics.“Pharmacogenomics”, as used herein, refers to the application ofgenomics technologies such as gene sequencing, statistical genetics, andgene expression analysis to drugs in clinical development and on themarket. More specifically, the term refers the study of how a patient'sgenes determine his or her response to a drug (e.g., a patient's “drugresponse phenotype”, or “drug response genotype”). Thus, another aspectof the invention provides methods for tailoring an individual'sprophylactic or therapeutic treatment with either the target MYC RNAmolecules of the present invention or target MYC RNA modulatorsaccording to that individual's drug response genotype. Pharmacogenomicsallows a clinician or physician to target prophylactic or therapeutictreatments to patients who will most benefit from the treatment and toavoid treatment of patients who will experience toxic drug-related sideeffects.

Therapeutic agents can be tested in a selected animal model. Forexample, a dsRNA agent (or expression vector or transgene encoding same)as described herein can be used in an animal model to determine theefficacy, toxicity, or side effects of treatment with said agent.Alternatively, an agent (e.g., a therapeutic agent) can be used in ananimal model to determine the mechanism of action of such an agent.

Models Useful to Evaluate the Down-Regulation of MYC mRNA Levels andExpression

Cell Culture

The dsRNA agents of the invention can be tested for cleavage activity invivo, for example, using the following procedure. The nucleotidesequences within the MYC cDNA targeted by the dsRNA agents of theinvention are shown in the above MYC sequences.

The dsRNA reagents of the invention can be tested in cell culture usingA549 or other mammalian cells to determine the extent of MYC RNA and Mycprotein inhibition. In certain embodiments, DsiRNA reagents (e.g., seeFIG. 1, and above-recited structures) are selected against the MYCtarget as described herein. MYC RNA inhibition is measured afterdelivery of these reagents by a suitable transfection agent to, forexample, cultured A549 cells or other transformed or non-transformedmammalian cells in culture. Relative amounts of target MYC RNA aremeasured versus actin or other appropriate control using real-time PCRmonitoring of amplification (e.g., ABI 7700 TAQMAN®). A comparison ismade to the activity of oligonucleotide sequences made to unrelatedtargets or to a randomized DsiRNA control with the same overall lengthand chemistry, or simply to appropriate vehicle-treated or untreatedcontrols. Primary and secondary lead reagents are chosen for the targetand optimization performed.

TAQMAN® (Real-Time PCR Monitoring of Amplification) and LightcyclerQuantification of mRNA

Total RNA is prepared from cells following DsiRNA delivery, for example,using Ambion Rnaqueous 4-PCR purification kit for large scaleextractions, or Promega SV96 for 96-well assays. For Taqman analysis,dual-labeled probes are synthesized with, for example, the reporter dyesFAM or VIC covalently linked at the 5′-end and the quencher dye TAMMYCAconjugated to the 3′-end. PCR amplifications are performed on, forexample, an ABI PRISM 7700 Sequence detector using 50 uL reactionsconsisting of 10 uL total RNA, 100 nM forward primer, 100 mM reverseprimer, 100 nM probe, 1×TaqMan PCR reaction buffer (PE-AppliedBiosystems), 5.5 mM MgCl2, 100 uM each dATP, dCTP, dGTP and dTTP, 0.2 URNase Inhibitor (Promega), 0.025 U AmpliTaq Gold (PE-Applied Biosystems)and 0.2 U M-MLV Reverse Transcriptase (Promega). The thermal cyclingconditions can consist of 30 minutes at 48° C., 10 minutes at 95° C.,followed by 40 cycles of 15 seconds at 95° C. and 1 minute at 60° C.Quantitation of target MYC mRNA level is determined relative tostandards generated from serially diluted total cellular RNA (300, 100,30, 10 ng/rxn) and normalizing to, for example, HPRT1 mRNA in eitherparallel or same tube TaqMan reactions.

Western Blotting

Cellular protein extracts can be prepared using a standard micropreparation technique (for example using RIPA buffer), or preferably, byextracting nuclear proteins by a method such as the NE-PER Nuclear andCytoplasmic Extraction kit (Thermo-Fisher Scientific). Cellular proteinextracts are run on Tris-Glycine polyacrylamide gel and transferred ontomembranes. Non-specific binding can be blocked by incubation, forexample, with 5% non-fat milk for 1 hour followed by primary antibodyfor 16 hours at 4° C. Following washes, the secondary antibody isapplied, for example (1:10,000 dilution) for 1 hour at room temperatureand the signal detected on a VersaDoc imaging system

In several cell culture systems, cationic lipids have been shown toenhance the bioavailability of oligonucleotides to cells in culture(Bennet, et al., 1992, Mol. Pharmacology, 41, 1023-1033). In oneembodiment, dsRNA molecules of the invention are complexed with cationiclipids for cell culture experiments. dsRNA and cationic lipid mixturesare prepared in serum-free OptimMEM (InVitrogen) immediately prior toaddition to the cells. OptiMEM is warmed to room temperature (about20-25° C.) and cationic lipid is added to the final desiredconcentration. dsRNA molecules are added to OptiMEM to the desiredconcentration and the solution is added to the diluted dsRNA andincubated for 15 minutes at room temperature. In dose responseexperiments, the RNA complex is serially diluted into OptiMEM prior toaddition of the cationic lipid.

Animal Models

The efficacy of anti-MYC dsRNA agents may be evaluated in an animalmodel Animal models of cancer and/or proliferative diseases, conditions,or disorders as are known in the art can be used for evaluation of theefficacy, potency, toxicity, etc. of anti-MYC dsRNAs. Suitable animalmodels of proliferative disease include, e.g., transgenic rodents (e.g.,mice, rats) bearing gain of function proto-oncogenes (e.g., Myc, Src)and/or loss of function of tumour suppressor proteins (e.g., p53, Rb) orrodents that have been exposed to radiation or chemical mutagens thatinduce DNA changes that facilitate neoplastic transformation. Many suchanimal models are commercially available, for example, from The JacksonLaboratory, Bar Harbor, Me., USA. These animal models may be used as asource cells or tissue for assays of the compositions of the invention.Such models can also be used or adapted for use for pre-clinicalevaluation of the efficacy of dsRNA compositions of the invention inmodulating MYC gene expression toward therapeutic use.

As in cell culture models, the most MYC relevant mouse tumor xenograftsare those derived from cancer cells that express Myc proteins. Xenograftmouse models of cancer relevant to study of the anti-tumor effect ofmodulating MYC have been described by various groups (e.g., Leonetti etal., J. NCI 1996 April; 88: 419; Iversen et al., Clin Cancer Res 2003July; 9: 2510; Devi et al., Clin Cancer Res 2005 May; 11: 3930; Chen etal., Mol Ther 2010 April; 18:828; Kessler et al., Science 2012 January;335: 348). Use of these models has demonstrated that inhibition of MYCexpression by anti-MYC agents causes inhibition of tumor growth inanimals.

Such models can be used in evaluating the efficacy of dsRNA molecules ofthe invention to inhibit MYC levels, expression, tumor/cancer formation,growth, spread, development of other MYC-associated phenotypes, diseasesor disorders, etc. These models and others can similarly be used toevaluate the safety/toxicity and efficacy of dsRNA molecules of theinvention in a pre-clinical setting.

Specific examples of animal model systems useful for evaluation of theMYC-targeting dsRNAs of the invention include wild-type mice, andorthotopic or subcutaneous HT1080, HCT116, SW480, SW620, Hep3B, M14,JR8, PLF2, LLC1, LNCaP, PC3, SUM159, MDAMB-231, 22Rv1, 518A2, MHCC97,A549, H1299, HepG2, SNU398, HuH7, NCI-H196, NCI-H1975, HT29, MKN-45,MDA-MB-231, NCI-H441, Panc-1, MIA PaCa-2, BxPC3, DU-145, M2182, VCaP,OvCar-3, MCF-7, U937, K562, HeLa, T98G, or SHP-77 tumor model mice. Inan exemplary in vivo experiment, dsRNAs of the invention are tail veininjected into such mouse models at doses ranging from 1 to 10 mg/kg or,alternatively, repeated doses are administered at single-dose IC₅₀levels, and organs (e.g., prostate, liver, kidney, lung, pancreas,colon, skin, spleen, bone marrow, lymph nodes, mammary fat pad, etc.)are harvested 24 hours after administration of the final dose. Suchorgans are then evaluated for mouse and/or human MYC levels, dependingupon the model used. Duration of action can also be examined at, e.g.,1, 4, 7, 14, 21 or more days after final dsRNA administration.

The practice of the present invention employs, unless otherwiseindicated, conventional techniques of chemistry, molecular biology,microbiology, recombinant DNA, genetics, immunology, cell biology, cellculture and transgenic biology, which are within the skill of the art.See, e.g., Maniatis et al., 1982, Molecular Cloning (Cold Spring HarborLaboratory Press, Cold Spring Harbor, N.Y.); Sambrook et al., 1989,Molecular Cloning, 2nd Ed. (Cold Spring Harbor Laboratory Press, ColdSpring Harbor, N.Y.); Sambrook and Russell, 2001, Molecular Cloning, 3rdEd. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.);Ausubel et al., 1992), Current Protocols in Molecular Biology (JohnWiley & Sons, including periodic updates); Glover, 1985, DNA Cloning(IRL Press, Oxford); Anand, 1992; Guthrie and Fink, 1991; Harlow andLane, 1988, Antibodies, (Cold Spring Harbor Laboratory Press, ColdSpring Harbor, N.Y.); Jakoby and Pastan, 1979; Nucleic AcidHybridization (B. D. Hames & S. J. Higgins eds. 1984); Transcription AndTranslation (B. D. Hames & S. J. Higgins eds. 1984); Culture Of AnimalCells (R. I. Freshney, Alan R. Liss, Inc., 1987); Immobilized Cells AndEnzymes (IRL Press, 1986); B. Perbal, A Practical Guide To MolecularCloning (1984); the treatise, Methods In Enzymology (Academic Press,Inc., N.Y.); Gene Transfer Vectors For Mammalian Cells (J. H. Miller andM. P. Calos eds., 1987, Cold Spring Harbor Laboratory); Methods InEnzymology, Vols. 154 and 155 (Wu et al. eds.), Immunochemical MethodsIn Cell And Molecular Biology (Mayer and Walker, eds., Academic Press,London, 1987); Handbook Of Experimental Immunology, Volumes I-IV (D. M.Weir and C. C. Blackwell, eds., 1986); Riott, Essential Immunology, 6thEdition, Blackwell Scientific Publications, Oxford, 1988; Hogan et al.,Manipulating the Mouse Embryo, (Cold Spring Harbor Laboratory Press,Cold Spring Harbor, N.Y., 1986); Westerfield, M., The zebrafish book. Aguide for the laboratory use of zebrafish (Danio rerio), (4th Ed., Univ.of Oregon Press, Eugene, 2000).

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present invention, suitable methods andmaterials are described below. All publications, patent applications,patents, and other references mentioned herein are incorporated byreference in their entirety. In case of conflict, the presentspecification, including definitions, will control. In addition, thematerials, methods, and examples are illustrative only and not intendedto be limiting.

EXAMPLES

The present invention is described by reference to the followingExamples, which are offered by way of illustration and are not intendedto limit the invention in any manner. Standard techniques well known inthe art or the techniques specifically described below were utilized.

Example 1 Preparation of Double-Stranded RNA Oligonucleotides

Oligonucleotide Synthesis and Purification

DsiRNA molecules can be designed to interact with various sites in theRNA message, for example, target sequences within the RNA sequencesdescribed herein. In presently exemplified agents, 327 human target MYCsequences and 144 mouse target MYC sequences were selected forevaluation (183 of the 327 human target MYC sites were predicted to beconserved with corresponding sites in the mouse MYC transcriptsequence). The sequences of one strand of the DsiRNA molecules werecomplementary to the target MYC site sequences described above. TheDsiRNA molecules were chemically synthesized using methods describedherein. Generally, DsiRNA constructs were synthesized using solid phaseoligonucleotide synthesis methods as described for 19-23mer siRNAs (seefor example Usman et al., U.S. Pat. Nos. 5,804,683; 5,831,071;5,998,203; 6,117,657; 6,353,098; 6,362,323; 6,437,117; 6,469,158;Scaringe et al., U.S. Pat. Nos. 6,111,086; 6,008,400; 6,111,086).

Individual RNA strands were synthesized and HPLC purified according tostandard methods (Integrated DNA Technologies, Coralville, Iowa). Forexample, RNA oligonucleotides were synthesized using solid phasephosphoramidite chemistry, deprotected and desalted on NAP-5 columns(Amersham Pharmacia Biotech, Piscataway, N.J.) using standard techniques(Damha and Olgivie, 1993, Methods Mol Biol 20: 81-114; Wincott et al.,1995, Nucleic Acids Res 23: 2677-84). The oligomers were purified usingion-exchange high performance liquid chromatography (IE-HPLC) on anAmersham Source 15Q column (1.0 cm×25 cm; Amersham Pharmacia Biotech,Piscataway, N.J.) using a 15 min step-linear gradient. The gradientvaries from 90:10 Buffers A:B to 52:48 Buffers A:B, where Buffer A is100 mM Tris pH 8.5 and Buffer B is 100 mM Tris pH 8.5, 1 M NaCl. Sampleswere monitored at 260 nm and peaks corresponding to the full-lengtholigonucleotide species are collected, pooled, desalted on NAP-5columns, and lyophilized.

The purity of each oligomer was determined by capillary electrophoresis(CE) on a Beckman PACE 5000 (Beckman Coulter, Inc., Fullerton, Calif.).The CE capillaries had a 100 μm inner diameter and contains ssDNA 100RGel (Beckman-Coulter). Typically, about 0.6 nmole of oligonucleotide wasinjected into a capillary, run in an electric field of 444 V/cm anddetected by UV absorbance at 260 nm Denaturing Tris-Borate-7 M-urearunning buffer was purchased from Beckman-Coulter. Oligoribonucleotideswere obtained that are at least 90% pure as assessed by CE for use inexperiments described below. Compound identity was verified bymatrix-assisted laser desorption ionization time-of-flight (MALDI-TOF)mass spectroscopy on a Voyager DE™ Biospectometry Work Station (AppliedBiosystems, Foster City, Calif.) following the manufacturer'srecommended protocol. Relative molecular masses of all oligomers wereobtained, often within 0.2% of expected molecular mass.

Preparation of Duplexes

Single-stranded RNA (ssRNA) oligomers were resuspended, e.g., at 100 μMconcentration in duplex buffer consisting of 100 mM potassium acetate,30 mM HEPES, pH 7.5. Complementary sense and antisense strands weremixed in equal molar amounts to yield a final solution of, e.g., 50 μMduplex. Samples were heated to 100° C. for 5′ in RNA buffer (IDT) andallowed to cool to room temperature before use. Double-stranded RNA(dsRNA) oligomers were stored at −20° C. Single-stranded RNA oligomerswere stored lyophilized or in nuclease-free water at −80° C.

Nomenclature

For consistency, the following nomenclature has been employed in theinstant specification. Names given to duplexes indicate the length ofthe oligomers and the presence or absence of overhangs. A “25/27” is anasymmetric duplex having a 25 base sense strand and a 27 base antisensestrand with a 2-base 3′-overhang. A “27/25” is an asymmetric duplexhaving a 27 base sense strand and a 25 base antisense strand.

Cell Culture and RNA Transfection

A549 cells were obtained from ATCC and maintained in DMEM (HyClone)supplemented with 10% fetal bovine serum (HyClone) at 37° C. under 5%CO₂. Hepa 1-6 cells were obtained from ATCC and maintained in DMEM(HyClone) supplemented with 10% fetal bovine serum (HyClone) at 37° C.under 5% CO₂. For RNA transfections, cells were transfected with DsiRNAsas indicated at a final concentration of 1 nM, 0.3 nM or 0.1 nM usingLipofectamine™ RNAiMAX (Invitrogen) and following manufacturer'sinstructions. Briefly, for 0.1 nM transfections, e.g., of Example 3below, an aliquot of stock solution of each DsiRNA was mixed withOpti-MEM I (Invitrogen) and Lipofectamine™ RNAiMAX to reach a volume of150 μL, (with 0.3 nM DsiRNA). The resulting 150 μL, mix was incubatedfor 20 min at RT to allow DsiRNA:Lipofectamine™ RNAiMAX complexes toform. Meanwhile, target cells were trypsinized and resuspended inmedium. At the end of the 20 min of complexation, 50 uL of theDsiRNA:RNAiMAX mixture was added per well into triplicate wells of 96well plates. Finally, 100 μL of the cell suspension were added to eachwell (final volume 150 μL) and plates were placed into the incubator for24 hours.

Assessment of MYC Inhibition

MYC target gene knockdown was determined by qRT-PCR, with valuesnormalized to HPRT and SFRS9 housekeeping genes, and to transfectionswith control DsiRNAs and/or mock transfection controls.

RNA Isolation and Analysis

Media was aspirated, and total RNA was extracted using the SV96 kit(Promega). Total RNA was reverse-transcribed using SuperscriptII, OligodT, and random hexamers following manufacturer's instructions.Typically, the resulting cDNA was analyzed by qPCR using primers andprobes specific for both the MYC gene and for the human genes HPRT-1 andSFRS9. An ABI 7700 was used for the amplification reactions. Each samplewas tested in triplicate. Relative MYC RNA levels were normalized toHPRT1 and SFRS9 RNA levels and compared with RNA levels obtained intransfection control samples.

Example 2 DsiRNA Inhibition of MYC

DsiRNA molecules targeting MYC were designed and synthesized asdescribed above and tested in human A549 cells or mouse Hepa 1-6 cellsfor inhibitory efficacy. For transfection, annealed DsiRNAs were mixedwith the transfection reagent (Lipofectamine™ RNAiMAX, Invitrogen) andincubated for 20 minutes at room temperature. The A549 (human) or Hepa1-6 (mouse) cells were trypsinized, resuspended in media, and added towells (100 uL per well) to give a final DsiRNA concentration of 1 nM ina volume of 150 μl. Each DsiRNA transfection mixture was added to 3wells for triplicate DsiRNA treatments. Cells were incubated at 37° C.for 24 hours in the continued presence of the DsiRNA transfectionmixture. At 24 hours, RNA was prepared from each well of treated cells.The supernatants with the transfection mixtures were first removed anddiscarded, then the cells were lysed and RNA prepared from each well.Target MYC RNA levels following treatment were evaluated by qRT-PCR forthe MYC target gene, with values normalized to those obtained forcontrols. Triplicate data was averaged and the % error determined foreach treatment. Normalized data were graphed and the reduction of targetmRNA by active DsiRNAs in comparison to controls was determined.

MYC targeting DsiRNAs examined for MYC inhibitory efficacy in an initialphase of testing are indicated in Table 8 below. In this example, 471asymmetric DsiRNAs (tested DsiRNAs possessed a 25/27mer structure) wereconstructed and tested for MYC inhibitory efficacy in human A549 andmouse Hepa 1-6 cells incubated in the presence of such DsiRNAs at aconcentration of 1 nM. The 471 asymmetric DsiRNAs tested in the initialscreen included DsiRNAs possessing 2′-O-methyl modified residues asshown in Tables 2 and 4 above, where underlined nucleotide residuesindicate 2′-O-methyl modified residues, ribonucleotide residues areshown as UPPER CASE, and deoxyribonucleotide residues are shown as lowercase.

Assay of the 471 MYC targeting DsiRNAs in human A549 and mouse Hepa 1-6cells at 1 nM revealed the following MYC inhibitory efficacies,presented in Tables 9 and 10. MYC levels were determined using qPCRassays positioned at indicated locations within the MYC transcript (forhuman A549 cell experiments, three distinct qPCR assays were performedand are indicated as “Hs MYC 514-620” (FAM), “Hs MYC 1227-1347” (MAX)and “Hs MYC 1771-1882” (MAX); for mouse Hepa 1-6 cell experiments, threedistinct qPCR assays were performed and are indicated as “Mm MYC539-663” (FAM), “Mm MYC 1339-1428” (MAX) and “Mm MYC 1971-2062” (MAX).

TABLE 9 MYC Inhibitory Efficacy of DsiRNAs Assayed at 1 nM in Human A549Cells and Mouse Hepa 1-6 Cells Human A549 Human A549 Human A549 CellsCells Cells % Remaining % Remaining % Remaining DsiRNA Name MYC mRNA ±MYC mRNA ± MYC mRNA ± (Human MYC % Error % Error % Error Target MouseMYC (Assay: Hs (Assay: Hs (Assay: Hs Location, Target Location MYC514-620 MYC 1227-1347 MYC 1771-1882 NM_002467.4) (NM_010849.4) (FAM))(MAX)) (MAX)) MYC-94 141.4 ± 4.5  155.9 ± 3   97.8 ± 2.6 MYC-178 78.9 ±3.6   72 ± 5.2 72.3 ± 2.2 MYC-365 135.3 ± 8.1   81.2 ± 11.6 86.4 ± 6.3MYC-370 64.5 ± 4.7 62.2 ± 12  74.4 ± 1.5 MYC-376 125.7 ± 6.7  86.6 ± 6  94.1 ± 5.3 MYC-403 98.2 ± 1.1 65.4 ± 6.5 76.2 ± 2.9 MYC-409 74.8 ± 5.371.1 ± 9.6 67.8 ± 4.2 MYC-417 120.2 ± 3.3  130.8 ± 2.2  97.2 ± 1.4MYC-535   82 ± 7.1 102.9 ± 7.6  92.9 ± 6.1 MYC-541 55.4 ± 3.2   66 ± 7.577.6 ± 4.3 MYC-548 41.7 ± 5.5   70 ± 2.2 71.9 ± 1.2 MYC-553 58.1 ± 8.5114.8 ± 11   84.8 ± 9.4 MYC-562 55.3 ± 6.5 83.6 ± 6.9 83.8 ± 0.9 MYC-601 33.3 ± 11.6  87.5 ± 12.1 81.6 ± 2.2 MYC-607   30 ± 6.2   55 ± 8.8 55.5± 1.4 MYC-643  69.1 ± 12.7 87.9 ± 17   79.4 ± 13.1 MYC-651 59.5 ± 8.971.4 ± 10  61.8 ± 4.6 MYC-676 57.2 ± 5.7 79.3 ± 6.4 89.3 ± 4.9 MYC-731 74.3 ± 10.9 101.4 ± 12.3 109.5 ± 5.7  MYC-816 85.9 ± 9.8  87.8 ± 19.883.6 ± 2.5 MYC-920 41.2 ± 4.1 61.7 ± 1.8 60.5 ± 2.3 MYC-949 39.2 ± 7.8 56.5 ± 10.1 70.7 ± 6.2 MYC-958  63.3 ± 11.8  93.9 ± 16.6 82.5 ± 6.5MYC-970 44.8 ± 2.4 52.4 ± 4.6 55.8 ± 5.1 MYC-987 81.7 ± 7.5  85.4 ± 10.279.8 ± 3.1 MYC-1104 87.3 ± 4.3 119.9 ± 4.1   75.4 ± 11.9 MYC-1111 49.6 ±7.5 95.9 ± 6.9 65.3 ± 4.8 MYC-1116 49.3 ± 0.8 65.6 ± 1.9 49.4 ± 4.9MYC-1210 73.6 ± 3.5 138.6 ± 4.4  87.1 ± 2.6 MYC-1340 46.5 ± 5.2 52.6 ±4.2   67 ± 14.7 MYC-1346 41.2 ± 4   38.1 ± 5.2   73 ± 14.9 MYC-1351 45.8 ± 10.5 42.9 ± 9.2 63.1 ± 3.2 MYC-1358 54.2 ± 6.1  61.9 ± 10.6 88.7± 2.1 MYC-1364 42.3 ± 4.8 39.1 ± 2.5 48.6 ± 5.4 MYC-1370 40.6 ± 1.7 31.3± 5.4 41.4 ± 5.4 MYC-1376 68.5 ± 4.3 57.8 ± 5.2 68.1 ± 0.8 MYC-1382 41.7± 1.5 33.2 ± 4.3 38.1 ± 1.2 MYC-1401   72 ± 5.8 71.2 ± 8.7 63.3 ± 5.6MYC-1406 118.6 ± 5   138.1 ± 9.3  96.3 ± 5.8 MYC-1411 92.7 ± 5.5 78.5 ±6.8 85.8 ± 2.8 MYC-1416 86.7 ± 5.7 77.4 ± 9.6 85.3 ± 7.5 MYC-1421 72.3 ±4.2 74.4 ± 3.9   74 ± 4.7 MYC-1457 47.3 ± 8.7  38.1 ± 14.1 52.3 ± 4.6MYC-1465 42.6 ± 8.3 28.7 ± 7.8 54.4 ± 4.1 MYC-1531 85.6 ± 1.7 71.2 ± 1  83.2 ± 5.8 MYC-1538 110.8 ± 6.4   104 ± 6.8 92.3 ± 7   MYC-1550 100.7 ±4     91 ± 5.5   91 ± 3.5 MYC-1555 56.2 ± 1.5 43.9 ± 4.3 91.5 ± 5.1MYC-1560 106.7 ± 7.6  99.2 ± 9.7 92.9 ± 9   MYC-1565 76.2 ± 6.3 87.2 ±7.3 87.6 ± 2.3 MYC-1570 70.3 ± 2.7 58.8 ± 1.2 64.2 ± 2   MYC-1575 60.4 ±5.7 52.4 ± 6.3 71.1 ± 4.4 MYC-1584 46.7 ± 3.1 32.5 ± 3   91.9 ± 4.9MYC-1593 78.8 ± 3.2 59.6 ± 4.2 104.3 ± 1.6  MYC-1599 53.6 ± 5.9 47.8 ±7     67 ± 6.3 MYC-1634 101.8 ± 9.5  126.4 ± 12.1 95.4 ± 1.9 MYC-163952.5 ± 1.9 47.8 ± 1.9 95.7 ± 3.1 MYC-1687 55.3 ± 5.3 47.1 ± 7.9 106.1 ±2.7  MYC-1693 66.1 ± 2.4 67.5 ± 1.6 82.9 ± 7.5 MYC-1698 36.3 ± 4.7 26.8± 5.5 34.9 ± 4   MYC-1704 83.7 ± 3.5 69.8 ± 18  77.1 ± 6.4 MYC-1709 55.5± 7.7 62.5 ± 12  102.8 ± 5.5  MYC-1729 65.9 ± 2.8 57.2 ± 3.3 65.9 ± 4.5MYC-1734 37.5 ± 1.4 32.6 ± 3.5 51.6 ± 2.4 MYC-1739 58.5 ± 3.4 50.3 ± 5.966.2 ± 4.3 MYC-1769 38.6 ± 3.1 32.5 ± 2.5 38.8 ± 3.4 MYC-1774 74.5 ± 3.476.4 ± 1   74.8 ± 0.7 MYC-1779 29.3 ± 2.7 32.6 ± 3.9 63.9 ± 4.6 MYC-178490.8 ± 2.7 98.5 ± 4.8 71.5 ± 5.6 MYC-1789   64 ± 7.4 59.1 ± 8.6 67.4 ±3.2 MYC-1795 44.3 ± 2.9 38.4 ± 5.3 48.9 ± 2.3 MYC-1803 71.2 ± 3   60.1 ±5.6 62.1 ± 3.6 MYC-1808 50.8 ± 3.4 41.1 ± 5   41.3 ± 5.8 MYC-1816   61 ±2.4 57.1 ± 4.5 65.2 ± 3.5 MYC-1823 40.9 ± 4.7 43.6 ± 7.6   38 ± 4.8MYC-1828 37.2 ± 2.9 31.7 ± 3.1 32.4 ± 2.7 MYC-1834 66.4 ± 1.8 68.4 ± 4.563.6 ± 7   MYC-1840 68.8 ± 3.9 67.9 ± 6.1 51.5 ± 3.1 MYC-1845 46.7 ± 5  38.7 ± 6.7 39.3 ± 2.5 MYC-1850 60.2 ± 8.9 52.7 ± 6.8   41 ± 5.6 MYC-185542.2 ± 2.6 34.2 ± 1.9 31.8 ± 2.8 MYC-1882 51.1 ± 7.1   46 ± 9.3 35.9 ±6   MYC-1888 100.1 ± 4.2  128.5 ± 3   86.6 ± 9.2 MYC-1893 68.8 ± 4.1  69 ± 1.9 47.6 ± 6.7 MYC-1900 60.7 ± 1.2 67.5 ± 3.7 53.3 ± 2   MYC-190663.8 ± 2.1 52 ± 7 61.5 ± 8.2 MYC-1911 41.7 ± 1.6 40.9 ± 1.4 35.5 ± 2.2MYC-1921 55.7 ± 3.2 44.3 ± 5.2 56.6 ± 4.7 MYC-1926 53.8 ± 4.7 59.6 ± 4.641.9 ± 6   MYC-1931 45.3 ± 3.7 38.9 ± 7.3 36.6 ± 2.6 MYC-1937 77.7 ± 5.575.3 ± 6.6 51.8 ± 5.3 MYC-1944 69.1 ± 5.9 66.7 ± 7.1 38.1 ± 7.6 MYC-1953104.8 ± 2.8  134.3 ± 2.7  57.7 ± 2.3 MYC-1959 109.7 ± 4.7  119.6 ± 4.1 62.2 ± 8.6 MYC-1965 59.4 ± 3.5 56.4 ± 7.3 35.9 ± 7.1 MYC-1970 67.6 ± 2.861.8 ± 3.1   47 ± 7.2 MYC-1976 77.8 ± 0.3 91.4 ± 0.8 47.1 ± 4.5 MYC-198192.2 ± 5.9 94.1 ± 7.7   47 ± 5.9 MYC-1989 60.2 ± 2.5 52.4 ± 3.3   38 ±2.8 MYC-1994 111.3 ± 2.7  149.4 ± 6.3  46.8 ± 3   MYC-2001  86.3 ± 10.7 92.5 ± 15.3 31.9 ± 2   MYC-2006 84.3 ± 5.1 82.6 ± 6   38.5 ± 2.4MYC-2013 90.2 ± 2   66.8 ± 4.6 32.7 ± 1.5 MYC-2019 73.4 ± 4.2 60.3 ± 6.952.5 ± 2.8 MYC-2026   75 ± 2.9 83.8 ± 4.4 48.2 ± 9.2 MYC-2031 76.1 ± 4.160.1 ± 5.2 49.7 ± 5.3 MYC-2040 73.3 ± 7.4 71.9 ± 12  33.4 ± 5.7 MYC-2048  88 ± 3.1 75.4 ± 4   45.9 ± 3.9 MYC-2054 118.4 ± 9.2  109.4 ± 9.1  77.4± 5.5 MYC-2059 80.8 ± 4.8 84.1 ± 3.8 57.9 ± 2.9 MYC-2066 62.7 ± 6   52.9± 5   38.9 ± 9.7 MYC-2073   76 ± 0.6 76.3 ± 0.3 43.2 ± 8.2 MYC-2078 94.8± 2.4 88.2 ± 3.6 66.6 ± 3.8 MYC-2083 76.5 ± 2.1 64.3 ± 3.4 32.3 ± 4  MYC-2089 85.8 ± 3.5 68.4 ± 5.4   54 ± 2.8 MYC-2094 69.7 ± 1.1 52.7 ± 4.9  33 ± 2.1 MYC-2099 60.1 ± 5.5 56.5 ± 6.5  30.4 ± 11.4 MYC-2105 81.6 ±5.5 87.8 ± 5   84.6 ± 7.5 MYC-2114 73.6 ± 7.7 57.9 ± 8.9 30.8 ± 3.1MYC-2120 60.1 ± 3.1 50.2 ± 9.1 27.3 ± 5.9 MYC-2128 72.8 ± 3   70.5 ± 2    52 ± 1.9 MYC-2135 81.1 ± 4   74.1 ± 7.6 65.6 ± 5.5 MYC-2167 100.1 ±6.3  100.6 ± 10.5 62.5 ± 1.6 MYC-2176 85.8 ± 6.2 73.5 ± 8.9 43.9 ± 6.2MYC-2181 76.1 ± 1.2 74.2 ± 3.3 59.7 ± 1.3 MYC-2188 80.2 ± 3   71.2 ± 3.934.4 ± 1   MYC-2207 80.3 ± 5.8 71.2 ± 9.3   58 ± 6.7 MYC-2233   72 ± 2.170.6 ± 1.9 39.1 ± 5.9 MYC-2260 86.9 ± 6.3 94.8 ± 9.6 50.7 ± 7.4 MYC-226799.8 ± 3.9 115.7 ± 3.1  83.6 ± 4.6 MYC-2274 92.3 ± 2.7 79.5 ± 5.8 81.8 ±3.6 MYC-2282  100 ± 5.5 121.4 ± 5.1    64 ± 15.8 MYC-2287 102.5 ± 5.3 91.1 ± 7   84.2 ± 3   MYC-2295 100.1 ± 4.2  109.6 ± 4.1  91.7 ± 5.2MYC-2300 73.2 ± 5.2 83.4 ± 3.4 43.5 ± 5.8 MYC-2306 57.6 ± 7.8 47.6 ± 9  40.1 ± 3.4 MYC-2312 100.1 ± 13.1 109.8 ± 15.4 70.7 ± 6.8 MYC-2334   94 ±5.8 86.2 ± 5.7 80.9 ± 5.3 MYC-2339 101.8 ± 1.5  100.4 ± 11.1 78.3 ± 0.6MYC-2347 71.9 ± 8.3  70.9 ± 11.7 60.7 ± 9.7 MYC-2355   72 ± 3.2 64.8 ±4.7 53.8 ± 3.3 MYC-2364 90.6 ± 5.8 84.1 ± 5.6 71.5 ± 5.4 MYC-2371 103.8± 5.9  100.6 ± 5.8  79.1 ± 2.9 MYC-2377 92.7 ± 1.9  116 ± 2.7 93.8 ± 2.5MYC-188 235 140.6 ± 7.7  197.8 ± 8.6  113.6 ± 3.9  MYC-189 236 110.6 ±2.5  137.3 ± 2   94.1 ± 4.1 MYC-190 237 129.5 ± 9.7  135.6 ± 11.3 90.3 ±3.8 MYC-191 238 119.5 ± 3   122.3 ± 2.9    83 ± 2.9 MYC-192 239 129.7 ±7.4  131.9 ± 10.1 93.9 ± 3.7 MYC-193 240 110.7 ± 2.5  120.4 ± 1.5    96± 2.2 MYC-194 241 131.7 ± 3.2  151.6 ± 3.7  103.1 ± 1.5  MYC-195 24295.5 ± 5   124.1 ± 5.3  86.2 ± 3.6 MYC-612 668 73.3 ± 4.1 123.5 ± 6.7 89.3 ± 1.8 MYC-613 669 72.3 ± 4.8 107.2 ± 6.2  79.9 ± 2   MYC-614 67098.9 ± 1.3 104.5 ± 5   73.2 ± 12  MYC-615 671 82.5 ± 5.1   83 ± 5.2 71.5± 2.7 MYC-616 672 68.4 ± 8.4 74.9 ± 8.7 69.2 ± 5.6 MYC-617 673 99.1 ±7.9 102.9 ± 8.1  89.6 ± 2.7 MYC-618 674 69.4 ± 3.5 96.7 ± 5.9 81.2 ± 3.1MYC-619 675 57.7 ± 3.8  103 ± 6.1 87.3 ± 5.2 MYC-620 676 80.1 ± 2.9  120± 4.2 102.6 ± 5   MYC-621 677 61.3 ± 5.2 126.8 ± 8.6  113.6 ± 3.1 MYC-622 678   36 ± 3.1 138.3 ± 4.8  124.4 ± 8.4  MYC-623 679 51.7 ± 2.481.2 ± 5.1 84.5 ± 4.1 MYC-624 680 67.1 ± 5.8 84.2 ± 7.7 80.5 ± 7.8MYC-625 681 69.4 ± 4.5 78.1 ± 5.4 75.7 ± 2.8 MYC-626 682 59.4 ± 3.2 65.9± 3.1 72.9 ± 5.6 MYC-627 683   66 ± 6.9  75.4 ± 13.4 80.8 ± 0.6 MYC-628684 128.9 ± 7.6  190.5 ± 9   112.7 ± 5.7  MYC-629 685 120.9 ± 3.9  157.4± 5.8  105.4 ± 1.6  MYC-733 789 95.9 ± 3.3 114.9 ± 6.3  99.9 ± 5.9MYC-734 790 86.3 ± 6.4 91.6 ± 7.4 84 ± 6 MYC-735 791 105.2 ± 4.3   105 ±2.7 90.3 ± 3.5 MYC-736 792 70.3 ± 7.5 79.8 ± 8.8 77.4 ± 8.2 MYC-737 793108.6 ± 3.7  124.3 ± 5.7  93.1 ± 3.1 MYC-738 794 116.3 ± 29.5 168.2 ±11.3 146.5 ± 2.6  MYC-739 795 97.2 ± 17  125.6 ± 11.7 111.3 ± 2  MYC-740 796 123.3 ± 7.5  138.2 ± 8.5  113 ± 3  MYC-741 797 88.2 ± 6.398.9 ± 7.6   90 ± 3.9 MYC-742 798 73.9 ± 7   84.7 ± 7.2 84.9 ± 3  MYC-743 799 97.6 ± 3.4 90.7 ± 5.6 106.3 ± 6.4  MYC-784 840 89.4 ± 6.981.6 ± 13  91.9 ± 3.3 MYC-785 841 89.5 ± 4.2 92.6 ± 4.1 96.9 ± 3.9MYC-786 842 93.1 ± 3.1 99.7 ± 5.7 97.5 ± 3.3 MYC-787 843 104.1 ± 11.3128.9 ± 12.7 107.7 ± 4.4  MYC-788 844  115 ± 1.1 126.7 ± 1   100.2 ± 3  MYC-913 972 55.8 ± 3.6 66.8 ± 7.2 80.1 ± 1.4 MYC-914 973 61.9 ± 3.9 63.2± 4.5 68.7 ± 5.6 MYC-915 974 64.1 ± 4   61.3 ± 6.1 82.5 ± 4.6 MYC-916975 69.5 ± 3.4 65.6 ± 2.7 81.1 ± 2.2 MYC-917 976 66.2 ± 8.4 68.1 ± 9  76.3 ± 3.2 MYC-952 1011 46.4 ± 4   70.6 ± 5.5 93.9 ± 1.9 MYC-953 101236.8 ± 4.2   67 ± 2.7 59.9 ± 9.1 MYC-973 1032  107 ± 8.2 122.6 ± 12  98.9 ± 2.6 MYC-974 1033 115.8 ± 4.3  126.4 ± 2.7  96.3 ± 2.4 MYC-9751034 103.1 ± 6.1  104.4 ± 13.2 94.3 ± 5.1 MYC-976 1035   86 ± 4.8 86.9 ±6.2 76.3 ± 4.4 MYC-977 1036 105.1 ± 2.9  104.8 ± 5.2  91.6 ± 2.6 MYC-9781037 104.5 ± 2   108.8 ± 4.6  91.5 ± 3.3 MYC-979 1038 113.8 ± 6.7  141.7± 3.1  104.7 ± 1   MYC-980 1039 122.8 ± 7.7  162.3 ± 9   105.9 ± 3.9 MYC-981 1040 85.5 ± 5.9   97 ± 7.5 81.1 ± 3.8 MYC-982 1041 123.1 ± 2.6 114.8 ± 9.7  102.3 ± 16.1 MYC-983 1042 105.6 ± 2.7  96.2 ± 2.8 89.4 ±4.6 MYC-984 1043 99.3 ± 5.2  90.1 ± 10.2 82.9 ± 4.6 MYC-985 1044 96.3 ±6.3 80.3 ± 4.8 90.8 ± 0.9 MYC-986 1045 86.6 ± 1.7   85 ± 7.1 86.2 ± 5.5MYC-1033 1092 100.3 ± 1.1  124.6 ± 3.2  100.7 ± 2.6  MYC-1034 1093 91.8± 4.9 118.3 ± 5.1  99.9 ± 4.8 MYC-1035 1094 110.9 ± 8.6  118.9 ± 11.4100.3 ± 4.2  MYC-1036 1095 109.1 ± 4.3  108.3 ± 5.6  90.4 ± 5.9 MYC-10371096 100.7 ± 5.6  90.1 ± 8.8 85.6 ± 3.1 MYC-1038 1097 110.6 ± 4   98.2 ±7.4 90.8 ± 3.2 MYC-1039 1098 98.1 ± 2.3   79 ± 2.6 93.9 ± 4.6 MYC-10401099 99.3 ± 5.9 90.3 ± 7.3 93.5 ± 4.9 MYC-1041 1100 89.3 ± 2.9 88.2 ±4.5 91.6 ± 3.7 MYC-1042 1101 104.2 ± 6.5  159.6 ± 8.5  104.7 ± 6.4 MYC-1043 1102 125.6 ± 4.8  150.1 ± 0.9  102.6 ± 3.9  MYC-1044 1103 95.7± 3    117 ± 6.3 83.9 ± 3.4 MYC-1045 1104 81 ± 4 106.8 ± 2.2  81.6 ± 3.8MYC-1046 1105 60.5 ± 4.4 101.5 ± 11.1 96.9 ± 5.8 MYC-1047 1106 86.3 ±5    102 ± 5.5 83.3 ± 5.6 MYC-1048 1107 98.9 ± 3.2 114.1 ± 7   86.7 ±7.7 MYC-1049 1108  85.6 ± 14.5  89.4 ± 10.4  80.4 ± 23.7 MYC-1050 110979.7 ± 1   102.3 ± 1.6    81 ± 1.5 MYC-1051 1110 106.2 ± 12.2 119.9 ±13.5 89.9 ± 7.5 MYC-1052 1111 98.6 ± 1.2 94.1 ± 2.4 78.1 ± 3   MYC-10531112 111.3 ± 5.2  103.5 ± 5.3  85.2 ± 4.3 MYC-1096 1155 98.3 ± 4.2 93.1± 5.9 87.8 ± 1.4 MYC-1097 1156 72.2 ± 5.1 101.5 ± 7.3  85.9 ± 5.2MYC-1098 1157 51.9 ± 3.7 103.4 ± 11.4 66.3 ± 2.5 MYC-1099 1158 73.9 ±9.5  92.5 ± 13.7 84.6 ± 3.1 MYC-1100 1159   64 ± 2.9 92.8 ± 4.7 83.5 ±6.7 MYC-1101 1160 104.2 ± 4.7  117.6 ± 6.3  100.8 ± 5.1  MYC-1189 1248  95 ± 4.4  110 ± 4.4 84.3 ± 4   MYC-1190 1249 95.1 ± 4.1 127.8 ± 7.2 84.5 ± 3.9 MYC-1191 1250 66.6 ± 1.5 212.4 ± 4.1  93.2 ± 2   MYC-11921251 62.3 ± 3.7 228.9 ± 4.2  92.6 ± 2.3 MYC-1193 1252 75.3 ± 2.7 118.2 ±2.7  74.7 ± 2.7 MYC-1315 1371 81.7 ± 2.3 50.3 ± 3.3 98.7 ± 5.1 MYC-13161372 127.1 ± 7.8  162.8 ± 7.6  106.3 ± 8.5  MYC-1317 1373 139.5 ± 5  154.7 ± 7.3  122.7 ± 4.3  MYC-1318 1374 123.7 ± 8.4  131.5 ± 12.8   97 ±3.5 MYC-1319 1375 121.9 ± 4.1  111.2 ± 4.7  93.1 ± 1.8 MYC-1320 1376126.1 ± 6.8  100.4 ± 6.1  111.9 ± 6.1  MYC-1321 1377 115.6 ± 4.2  108.8± 5.1  100.8 ± 5.7  MYC-1322 1378 106.2 ± 6.3  108.1 ± 6.2  93.1 ± 7  MYC-1323 1379 99.5 ± 5.9 113.5 ± 7.8  102.4 ± 3.8  MYC-1324 1380 118.1 ±3.8  144.1 ± 5.5  101.9 ± 3.9  MYC-1325 1381 139.3 ± 5   155.5 ± 5.5 119.6 ± 5.5  MYC-1326 1382 152.2 ± 3.9  100.2 ± 16.7 138.1 ± 5.1 MYC-1327 1383 91.8 ± 2.4 60.8 ± 3.6 79.2 ± 3.6 MYC-1328 1384 91.2 ± 2.474.6 ± 2.7   82 ± 2.1 MYC-1329 1385 79.9 ± 6.9 64.1 ± 8.6 76.9 ± 1.8MYC-1330 1386   78 ± 2.8 67.3 ± 3.8 73.6 ± 7   MYC-1331 1387 95.2 ± 2  100.4 ± 1.7  97.3 ± 2.9 MYC-1332 1388 75.4 ± 4.7 78.9 ± 6.4 79.9 ± 3.6MYC-1333 1389 59.2 ± 1.5 50.1 ± 1.9 67.8 ± 2.3 MYC-1334 1390 76.2 ± 1.164.9 ± 3.7   75 ± 5.2 MYC-1360 1416 37.5 ± 6.2 25.7 ± 6.8 47.5 ± 3.8MYC-1361 1417 79.4 ± 3.3 64.6 ± 1.7 81.8 ± 2   MYC-1448 1504 81.4 ± 6.468.9 ± 5.9 83.4 ± 2.4 MYC-1468 1524 37.4 ± 2.5 25.6 ± 3.9 50.4 ± 4.9MYC-1469 1525 74.7 ± 4.9 63.6 ± 9.8 81.4 ± 5.3 MYC-1470 1526 93.3 ± 5.3114.6 ± 9.6    94 ± 5.4 MYC-1471 1527 127.8 ± 6.8  144.6 ± 12.4 115.4 ±5.9  MYC-1472 1528 102.1 ± 2.1  110.3 ± 9.2  91.4 ± 2.7 MYC-1473 152984.8 ± 7.1 73.3 ± 9.2 86.2 ± 3.9 MYC-1474 1530 111.4 ± 3.2   113 ± 6.2106.6 ± 9.3  MYC-1475 1531 86.9 ± 6.5  92.1 ± 11.9 88.1 ± 4.2 MYC-14761532 80.7 ± 7.1  89.1 ± 10.3 85.7 ± 6.5 MYC-1477 1533 68.9 ± 7.4  89.1 ±18.1 99.3 ± 5.9 MYC-1478 1534 109.1 ± 2   144 ± 15 113.5 ± 1.8  MYC-14791535 105.1 ± 8.8  118.7 ± 8.6  106.9 ± 4.6  MYC-1480 1536 96.1 ± 2.698.5 ± 6.6 102.1 ± 2.5  MYC-1481 1537 102.7 ± 1.7    91 ± 6.9 96.5 ± 6.2MYC-1482 1538 55.2 ± 2.1  40.2 ± 10.1 99.4 ± 2.8 MYC-1483 1539 33.7 ±1.6 22.7 ± 12  108.6 ± 1.8  MYC-1711 1767 31.1 ± 4.8   25 ± 11.4 113.8 ±2.5  MYC-1712 1768 36.1 ± 6.7 32.8 ± 8.7 144.5 ± 4.5  MYC-1713 1769 75.1± 3.5 88.7 ± 4.1 83.7 ± 4.5 MYC-1714 1770 70.5 ± 6.6  78.1 ± 14.9 72 ± 3MYC-1715 1771   72 ± 1.7 73.2 ± 5.1   63 ± 4.8 MYC-1716 1772 72.2 ± 2.365.9 ± 8.2 68.5 ± 2.8 MYC-1717 1773 94.8 ± 5.5 78.8 ± 6.2 84.2 ± 3.7MYC-1718 1774 91.2 ± 3.3  76.4 ± 16.5 79.8 ± 2.1 MYC-1719 1775 96.5 ±6.8  89.8 ± 16.2 95.1 ± 4.6 MYC-1720 1776 80.8 ± 7    84.3 ± 14.3  89.3± 10.8 MYC-1721 1777 120.7 ± 12.9 155.7 ± 21.3 108.4 ± 5.7  MYC-18561912 97 ± 5 116.8 ± 6.4  68.4 ± 3.3 MYC-1857 1913 79.9 ± 3.5   77 ± 7.564.4 ± 1.2 MYC-2115 2195 86.8 ± 6.8  79.7 ± 12.5 41.3 ± 2.3 MYC-21162196 106.4 ± 4.1  107.8 ± 6.8   77.7 ± 17.1 MYC-2193 2273 119.9 ± 3.3 125.2 ± 8.9  91.5 ± 2.9 MYC-2194 2274 125.6 ± 2.7  141.2 ± 2.8  85.4 ±5.4 MYC-2195 2275 106.4 ± 8.4  136.6 ± 13.7 74.4 ± 2.8 MYC-2196 2276 101 ± 5.5 117.2 ± 4.9  46.3 ± 3.5 MYC-2197 2277 114.6 ± 3.9  131.3 ±3.4  59.1 ± 1.1 MYC-2198 2278 109.5 ± 7.9  122.6 ± 17.2 95.1 ± 4.1MYC-2199 2279 89 ± 6 73.8 ± 6.5 74.7 ± 4.7 MYC-2200 2280 110.2 ± 2.1 104.6 ± 2   79.7 ± 2   MYC-2201 2281 98.5 ± 5.9 89.2 ± 6     71 ± 3.8MYC-2202 2282 108.7 ± 5.4  103.2 ± 5.8  81.3 ± 2.8 MYC-2203 2283 107.3 ±3.9  118.3 ± 6.7  94.8 ± 3.8 MYC-2204 2284 117.1 ± 4   144.2 ± 4   96.4± 2.7 MYC-2205 2285 92.7 ± 5.1   97 ± 5.6   81 ± 9.6 MYC-2313 2363 88.9± 3   79.1 ± 2.8 88.5 ± 3.6 MYC-2314 2364 99.5 ± 2.9 89.1 ± 4.9 95.1 ±4.9 MYC-2315 2365 108.9 ± 5.8  96.1 ± 8.7 92.5 ± 5.4 MYC-2316 2366 78.8± 3     67 ± 3.5 80.8 ± 1.3 MYC-2317 2367 90.3 ± 2.9 81.6 ± 2.7 86.7 ±1.7 MYC-2318 2368  93.8 ± 11.4  85.2 ± 11.5 87.9 ± 6.2 MYC-2319 2369125.9 ± 4.7  160.6 ± 6.7  104.6 ± 4   MYC-2320 2370 139.2 ± 5.4   159 ±4.2 102.1 ± 4.8  MYC-2321 2371  108 ± 3.5 104.5 ± 3.9  69.4 ± 4.4MYC-2322 2372 143.6 ± 2   136.9 ± 5.4  102.3 ± 2.1  MYC-2323 2373 173.9± 4.7  160.6 ± 4.8  122 ± 5  MYC-2324 2374 124.6 ± 3.6  116.6 ± 5.2 89.6 ± 3.9 MYC-2325 2375  111 ± 3.3 127.5 ± 2.8  88.8 ± 3   MYC-23262376 122.9 ± 4   160.8 ± 6.3  122.7 ± 2.8  MYC-2327 2377 117.7 ± 12.7145.8 ± 14.4 110.8 ± 2.7  MYC-2328 2378 115.6 ± 5.6  125.5 ± 8    101 ±1.8 MYC-2329 2379  127 ± 6.8  86.7 ± 32.9 98.1 ± 0.6 MYC-2330 2380 104.8± 2.8  86.7 ± 2.8 90.7 ± 1.8 MYC-2331 2381 107.4 ± 3.2  97.6 ± 4.7  94.9± 10.4 MYC-2332 2382 115.8 ± 3.7   115 ± 5.9 99.7 ± 0.9 MYC-2333 238396.4 ± 1.6  96.5 ± 11.9 94.2

TABLE 10 MYC Inhibitory Efficacy of DsiRNAs Assayed at 1 nM in MouseHepa 1-6 Cells Mouse Hepa 1-6 Mouse Hepa 1-6 Mouse Hepa 1-6 Cells CellsCells % Remaining % Remaining % Remaining DsiRNA Name MYC mRNA ± MYCmRNA ± MYC mRNA ± (Human MYC % Error % Error % Error Target Mouse MYC(Assays: Mm (Assays: Mm (Assays: Mm Location, Target Location MYC539-663 MYC 1339-1428 MYC 1971-2062 NM_002467.4) (NM_010849.4) (FAM))(MAX)) (MAX)) MYC-188 235 129.1 ± 12.1 175.7 ± 9.3  104.5 ± 12.9 MYC-189236 118.2 ± 2.3  152.2 ± 5.6  97.1 ± 1.8 MYC-190 237 117.7 ± 2.5  127.1± 3.8  98.8 ± 4.4 MYC-191 238 110.3 ± 5    118 ± 2.6 99.1 ± 3.2 MYC-192239 98.9 ± 4.1 98.8 ± 6.4 83.5 ± 3.8 MYC-193 240 96.1 ± 1.9 102.6 ± 3.3 83.9 ± 0.9 MYC-194 241 108.7 ± 3.5  119.6 ± 2.9  91.7 ± 4.2 MYC-195 242136.9 ± 25.9 140.2 ± 12.1 81.4 ± 8.1 MYC-612 668 71.8 ± 4.6  122 ± 3.985.2 ± 2.1 MYC-613 669 81.4 ± 2.1 114.2 ± 3.5  93.7 ± 3.1 MYC-614 670108.8 ± 5.9  113.5 ± 1.4  93.2 ± 2.3 MYC-615 671 73.4 ± 8.7  76.9 ± 10.784.5 ± 2.6 MYC-616 672 65.5 ± 2.8 66.3 ± 3.5 72.8 ± 3.9 MYC-617 673 90.6± 1.6 96.3 ± 4.2 100.2 ± 2.1  MYC-618 674 56.3 ± 1.1 81.1 ± 5.1 80.4 ±2.3 MYC-619 675 63.7 ± 2.5 99.1 ± 4     86 ± 2.4 MYC-620 676 78.7 ± 9.9125.9 ± 10.4   99 ± 0.8 MYC-621 677 67.9 ± 5.9 155.1 ± 8.3  116.4 ± 5.9 MYC-622 678   67 ± 3.5 239.3 ± 4.2  178.6 ± 7.7  MYC-623 679 61.2 ± 5.999.6 ± 8.4 103 ± 5  MYC-624 680 70.7 ± 4.1 77.3 ± 8.7 88.7 ± 3.4 MYC-625681 73.8 ± 4.9 74.3 ± 2.2 86.9 ± 3   MYC-626 682 63.1 ± 6.8 68.6 ± 5.581 ± 3 MYC-627 683 76.8 ± 8.6  81.3 ± 10.9 89 ± 2 MYC-628 684 134.9 ±10.7 175.8 ± 9.8  117.2 ± 6.7  MYC-629 685 89.3 ± 2.5 122.8 ± 5.1  80.4± 2.2 MYC-733 789 69.2 ± 2   95.3 ± 4.3 75.2 ± 0.8 MYC-734 790   72 ±1.7 79.5 ± 2.6 75.7 ± 1.5 MYC-735 791 92.8 ± 2.1 94.7 ± 4   86.4 ± 1.7MYC-736 792 65.4 ± 2.6 76.9 ± 1.7 71.5 ± 2.4 MYC-737 793 99.7 ± 3.7121.4 ± 4.8  88.4 ± 5.5 MYC-738 794 139.9 ± 21   158.8 ± 20.7   83 ± 6.2MYC-739 795 97.7 ± 4.5 135.9 ± 1.3  96.7 ± 1   MYC-740 796 99.9 ± 3.6122.7 ± 4.3  94.6 ± 1.8 MYC-741 797   84 ± 8.4 78.3 ± 20    85 ± 4.7MYC-742 798 66.4 ± 4.3   83 ± 1.3 83.8 ± 2.7 MYC-743 799 89.6 ± 2   90.5± 2.9   96 ± 1.1 MYC-784 840 85.3 ± 3.9 91.7 ± 5.1 83.3 ± 0.8 MYC-785841 89.7 ± 2.7 106.1 ± 4.5  89.5 ± 0.9 MYC-786 842 96.6 ± 1.6 111.9 ±3.8  90.5 ± 2.2 MYC-787 843 105.1 ± 4.1  131.5 ± 7.8   111 ± 0.8 MYC-788844 107.6 ± 4.7  118.2 ± 5.5  101.6 ± 5.2  MYC-913 972 57.9 ± 4   74.3 ±3.7 82.7 ± 6.8 MYC-914 973 71.1 ± 6.5 69.9 ± 5   90.3 ± 5.1 MYC-915 97485.2 ± 1.4 81.6 ± 1.2 86.8 ± 0.7 MYC-916 975 81.9 ± 2.6   79 ± 2.9 85.3± 3.8 MYC-917 976 69.6 ± 2.6 74.1 ± 3.5 82.1 ± 3.5 MYC-952 1011 49.6 ±1.9 65.1 ± 3.9 69.6 ± 2   MYC-953 1012 37.7 ± 4.1 68.3 ± 7   44.7 ± 4.6MYC-973 1032 102.4 ± 3.6  126.9 ± 9.2  94.5 ± 2.3 MYC-974 1033 125.1 ±1.7  136.1 ± 4.3  90.7 ± 1.5 MYC-975 1034 89.8 ± 6.6 93.4 ± 9.1 79.6 ±3.4 MYC-976 1035 86.3 ± 3.7 82.8 ± 3.8 78.4 ± 3.6 MYC-977 1036  106 ±5.4 115.3 ± 2.1  89.4 ± 2.4 MYC-978 1037   99 ± 2.4 108.9 ± 2.1  81.4 ±2.8 MYC-979 1038 102.2 ± 7.2  120.2 ± 8.4  79.4 ± 6.9 MYC-980 1039 101.2± 3.3  137.3 ± 6.5  90.7 ± 3   MYC-981 1040 90.8 ± 3.6 111.5 ± 5.7    74± 0.9 MYC-982 1041   93 ± 3.6 89.5 ± 4.4 71.8 ± 3.4 MYC-983 1042 102.3 ±1.6  96.3 ± 4.3 83.3 ± 1.4 MYC-984 1043 98.3 ± 2.1 86.4 ± 2.6 82.1 ± 1.1MYC-985 1044 96.8 ± 4   96.8 ± 7     82 ± 4.8 MYC-986 1045 96.1 ± 6.298.4 ± 9.3 77.1 ± 3.1 MYC-1033 1092   91 ± 13.7 104.3 ± 23.2 80.5 ± 7  MYC-1034 1093 69.3 ± 4.6 86.7 ± 7.1 67.8 ± 1.9 MYC-1035 1094 99.1 ± 5.3111.7 ± 8     92 ± 7.6 MYC-1036 1095 112.5 ± 2.6  101.7 ± 6.2  90.7 ±1.7 MYC-1037 1096 122.1 ± 2.4  101.7 ± 3.8   116 ± 2.3 MYC-1038 1097101.7 ± 3.7  90.9 ± 3.4 87.6 ± 2.2 MYC-1039 1098 93.4 ± 3   85.8 ± 2.284.9 ± 2.9 MYC-1040 1099 93.4 ± 4.6   83 ± 8.6 87.7 ± 2.9 MYC-1041 110070.6 ± 4.7 62.5 ± 7.4 76.1 ± 3.3 MYC-1042 1101 115.5 ± 6.6  161.8 ± 7.5 110.7 ± 7   MYC-1043 1102 149.5 ± 2.7  184.3 ± 6.8  128.7 ± 1.3 MYC-1044 1103 127.6 ± 4.6  232.3 ± 8.5  136.8 ± 4.5  MYC-1045 1104 106.6± 2.7  279.5 ± 8   156.8 ± 4.4  MYC-1046 1105 106.6 ± 7.8  445.6 ± 15.4229.5 ± 6.9  MYC-1047 1106 118.2 ± 5.7   173 ± 6.7 128.8 ± 5.5  MYC-10481107  109 ± 2.4  130 ± 3.9 95.8 ± 2.1 MYC-1049 1108 107.1 ± 5.1  133.6 ±5.4  104.7 ± 2.3  MYC-1050 1109 70.4 ± 5.1 146.1 ± 6.6   111 ± 3.8MYC-1051 1110 97.3 ± 3.9 115.3 ± 3.9  99.6 ± 1.4 MYC-1052 1111 95.6 ±2.5 105.2 ± 2     90 ± 7.1 MYC-1053 1112 113.4 ± 2.8  116.8 ± 4   104 ±4  MYC-1096 1155 99.6 ± 1.7 132.5 ± 5.5  107 ± 5  MYC-1097 1156 89.1 ±3.8 188.9 ± 5   120.8 ± 3   MYC-1098 1157 68.4 ± 3.5 215.7 ± 3.1   117 ±5.6 MYC-1099 1158 68.9 ± 6.9 123.2 ± 9.3  91.1 ± 6.4 MYC-1100 1159 75.2± 1.6  212 ± 4.4 109.6 ± 1.2  MYC-1101 1160 101.3 ± 4.5  132.7 ± 1.3 74.8 ± 33  MYC-1189 1248 136.1 ± 5.6  168.5 ± 11.1 115.9 ± 11.5 MYC-11901249 95.8 ± 5.8 166.8 ± 6.8  116.4 ± 4.4  MYC-1191 1250 109.7 ± 9.1 647.4 ± 6.4  213.7 ± 9.8  MYC-1192 1251 105.8 ± 9   589.1 ± 9.1  221.4 ±13.9 MYC-1193 1252 96.9 ± 3.6 238.3 ± 5   126.7 ± 4.4  MYC-1315 137196.3 ± 7.6  92.2 ± 12.2 107.4 ± 6.4  MYC-1316 1372  110 ± 8.2 136 ± 6 111 ± 5  MYC-1317 1373 100.9 ± 2.9  107.1 ± 2.9  103.2 ± 5.6  MYC-13181374 104.2 ± 2.4  116.2 ± 3.6    99 ± 2.9 MYC-1319 1375 94.4 ± 3.2 86.5± 5.5 90.1 ± 1.4 MYC-1320 1376 96.6 ± 2.6 79.7 ± 1.2  104 ± 2.2 MYC-13211377 96.7 ± 3.7 103.6 ± 4.9  93.5 ± 2.3 MYC-1322 1378 106.8 ± 2.8  115.6± 4.5  97.6 ± 3.1 MYC-1323 1379 107.8± 115.6± 86.8± MYC-1324 1380 112.1± 2.7  139.1 ± 0.9  108.1 ± 2.5  MYC-1325 1381 103.3 ± 2.2  120.6 ± 2.5 100.5 ± 4.1  MYC-1326 1382   86 ± 3.9   66 ± 15.6   85 ± 2.3 MYC-13271383 77.4 ± 8.3 68.4 ± 8.8 82.2 ± 5.9 MYC-1328 1384 76.4 ± 2.2 70.5 ±2.3   78 ± 1.7 MYC-1329 1385 77.6 ± 7.1 78.1 ± 5.2 89.1 ± 8.3 MYC-13301386 75.2 ± 6.7 80.2 ± 7.2 79.9 ± 2.5 MYC-1331 1387 88.8 ± 5.3 94.7 ±7.5   83 ± 5.1 MYC-1332 1388   74 ± 4.7 84.2 ± 5.9 94.4 ± 3.2 MYC-13331389 65.1 ± 0.9 59.5 ± 2.2 108 ± 3  MYC-1334 1390 66.3 ± 4.8   62 ± 4.176.1 ± 3.6 MYC-1360 1416 41.6 ± 3.5   35 ± 2.5 55.3 ± 1.9 MYC-1361 141755.7 ± 2.2 54.8 ± 3.1 62.1 ± 2.2 MYC-1448 1504 83.1 ± 6.2 89.6 ± 4.287.5 ± 1.8 MYC-1468 1524 50.2 ± 2.1 47.6 ± 1.6 99.5 ± 2.1 MYC-1469 152568.8 ± 4.8  64.9 ± 10.8 72.5 ± 5.1 MYC-1470 1526 98.5 ± 7.5  93 ± 1076.6 ± 5.7 MYC-1471 1527 110.8 ± 5.6  120.5 ± 5.9  84.9 ± 3.8 MYC-14721528 107.2 ± 6.1  107.9 ± 6.8  82 ± 5 MYC-1473 1529 101.3 ± 9.3  97.1 ±7.4 83.5 ± 6.7 MYC-1474 1530 97.4 ± 1.9 88.8 ± 2.7 81.1 ± 3.6 MYC-14751531 128.5 ± 5.3  132.9 ± 6.6  101.6 ± 4.5  MYC-1476 1532 91.9 ± 6  90.8 ± 6.4 85.2 ± 4.7 MYC-1477 1533  93.6 ± 11.7   93 ± 7.1  93.7 ± 10.2MYC-1478 1534 97.6 ± 9.9 109.2 ± 8.8  90.6 ± 12  MYC-1479 1535 102.8 ±1.9  105.9 ± 3.7  105.3 ± 3.1  MYC-1480 1536 93.9 ± 5.8 90.2 ± 8.8  96.1± 10.2 MYC-1481 1537 112.4 ± 8   111.7 ± 5   102.7 ± 8.2  MYC-1482 1538 92.3 ± 10.9  88.8 ± 13.6   169 ± 12.9 MYC-1483 1539  65 ± 14  61.4 ±13.9   207 ± 14.3 MYC-1711 1767 59.9 ± 1.7 58.3 ± 4.8 180.3 ± 9.3 MYC-1712 1768 56.5 ± 3   57.6 ± 2.2 175.4 ± 6.7  MYC-1713 1769 86.2 ±3.7   97 ± 3.8 92.6 ± 2.6 MYC-1714 1770 104.4 ± 4.7  110.1 ± 3.2  92.4 ±3.4 MYC-1715 1771 98.9 ± 5.3 97.4 ± 6.9 89.8 ± 3.5 MYC-1716 1772 103.2 ±1.6  89.7 ± 2.5 92.1 ± 2.2 MYC-1717 1773 105.9 ± 4.7  85.5 ± 3.9 102.7 ±1.9  MYC-1718 1774 140.1 ± 12.4 152.3 ± 14.2 98.7 ± 5.6 MYC-1719 1775122.6 ± 5.6  118.9 ± 8.4  101.4 ± 3.8  MYC-1720 1776  82.9±  82.9± 72.9±MYC-1721 1777 108.3 ± 5.7  157.7 ± 6.4  103.2 ± 6.7  MYC-1856 1912 66.5± 4.3 86.9 ± 2.9 75.2 ± 4.8 MYC-1857 1913 60.9 ± 5.7   68 ± 7.2 74.6 ±2   MYC-2115 2195 79.7 ± 3.2 84.2 ± 1.8 54.3 ± 2.7 MYC-2116 2196 96.7 ±3.5 100.2 ± 3.9  77 ± 3 MYC-2193 2273 101.9 ± 2.4  112.2 ± 2.8  92.3 ±1   MYC-2194 2274 115.9 ± 4.1  143.8 ± 1.8  102.5 ± 2.8  MYC-2195 2275140.5 ± 20.6 175.2 ± 23.4 74.1 ± 5.9 MYC-2196 2276   89 ± 2.5 133.5 ±4   50.5 ± 3.7 MYC-2197 2277 79.2 ± 1.7 98.3 ± 5   56.3 ± 1.7 MYC-21982278 104.9 ± 8.5  129.9 ± 4.6  96.4 ± 2.4 MYC-2199 2279 68.5 ± 8.7 69.4± 4.6 54.7 ± 2.1 MYC-2200 2280 79.8 ± 1.7 80.1 ± 1.8 73.1 ± 1.9 MYC-22012281 74.3 ± 2.3 80.5 ± 1.8 63.5 ± 1.2 MYC-2202 2282 92.6 ± 2.4 106.6 ±6.4  81.2 ± 2   MYC-2203 2283 98.4 ± 3.2 116.2 ± 2.5  86.4 ± 2.9MYC-2204 2284 100.3 ± 1.3  134.4 ± 1.3  98.2 ± 6.2 MYC-2205 2285 82.8 ±5.4 91.1 ± 7   69.7 ± 5.6 MYC-2313 2363 95.7 ± 4.3 90.2 ± 6.2 91.8 ± 0.8MYC-2314 2364 96.8 ± 5   84.5 ± 5.6 85.4 ± 5.9 MYC-2315 2365 108.3 ±8.4  100.9 ± 8.7  104.6 ± 3.4  MYC-2316 2366 112.2 ± 4.1  104.2 ± 4.1  105 ± 2.5 MYC-2317 2367 99.6 ± 2.9 102.5 ± 2.8  98.4 ± 3.8 MYC-23182368 94.5 ± 5.5 96.2 ± 7.1 90 ± 6 MYC-2319 2369 123.4 ± 5.2  182.8 ±6.8  106.4 ± 10.7 MYC-2320 2370 108.6 ± 4.6  147.1 ± 3   88.7 ± 5.2MYC-2321 2371 89.6 ± 3.2 103.8 ± 5.9  67.7 ± 1.7 MYC-2322 2372   81 ±1.3   86 ± 1.2 75.1 ± 1.5 MYC-2323 2373 84.3 ± 2.5 85.5 ± 5.5 78.3 ± 2.6MYC-2324 2374 116.3 ± 2.9  137.2 ± 3.9   107 ± 4.3 MYC-2325 2375  117 ±6.5 147.2 ± 3.4  101.3 ± 2.4  MYC-2326 2376 119.8 ± 6.4  154.9 ± 2.1 98.9 ± 2.3 MYC-2327 2377 115.9 ± 4.5  162.4 ± 3.4   105 ± 1.9 MYC-23282378 123.1 ± 0.9  150.5 ± 3.5  111.8 ± 1   MYC-2329 2379 119.8 ± 8.1 125.5 ± 6.5  102.5 ± 3.4  MYC-2330 2380  105 ± 1.7 106.1 ± 1.6  96.8 ±3.5 MYC-2331 2381 108.7 ± 4.1  99.5 ± 6.2 99.4 ± 3.5 MYC-2332 2382 111.3± 2.5  123.9 ± 6.5  109.6 ± 4.3  MYC-2333 2383 108.7 ± 1.4  130.4 ± 6.8 99.1 ± 1.3 MYC-m187 129.1 ± 12.1 175.7 ± 9.3  119.3 ± 3.6  MYC-m194118.2 ± 2.3  152.2 ± 5.6  109.2 ± 6.7  MYC-m199 117.7 ± 2.5  127.1 ±3.8  94.1 ± 9.2 MYC-m210 110.3 ± 5    118 ± 2.6 120.7 ± 8.4  MYC-m22398.9 ± 4.1 98.8 ± 6.4 123.6 ± 1.9  MYC-m265 96.1 ± 1.9 102.6 ± 3.3  72.4± 3.4 MYC-m273 108.7 ± 3.5  119.6 ± 2.9   117 ± 3.7 MYC-m321 136.9 ±25.9 140.2 ± 12.1 86.1 ± 6.8 MYC-m384 71.8 ± 4.6  122 ± 3.9 100.9 ± 1.2 MYC-m455 81.4 ± 2.1 114.2 ± 3.5  79.3 ± 4   MYC-m460 108.8 ± 5.9  113.5± 1.4  75.1 ± 3.2 MYC-m469 73.4 ± 8.7  76.9 ± 10.7 85.3 ± 7.1 MYC-m47865.5 ± 2.8 66.3 ± 3.5 202.5 ± 5.2  MYC-m581 90.6 ± 1.6 96.3 ± 4.2 64.6 ±3.1 MYC-m591 56.3 ± 1.1 81.1 ± 5.1 92.5 ± 2.4 MYC-m597 63.7 ± 2.5 99.1 ±4     81 ± 3.2 MYC-m609 78.7 ± 9.9 125.9 ± 10.4 78.7 ± 1.6 MYC-m657 67.9± 5.9 155.1 ± 8.3  75.6 ± 2.5 MYC-m663   67 ± 3.5 239.3 ± 4.2  106.2 ±3   MYC-m699 61.2 ± 5.9 99.6 ± 8.4 106.2 ± 0.7  MYC-m724 70.7 ± 4.1 77.3± 8.7 58.1 ± 4.7 MYC-m732 73.8 ± 4.9 74.3 ± 2.2 97.6 ± 5.1 MYC-m787 63.1± 6.8 68.6 ± 5.5 89.9 ± 5.3 MYC-m800 76.8 ± 8.6  81.3 ± 10.9 65.6 ± 7.3MYC-m852 134.9 ± 10.7 175.8 ± 9.8  82.5 ± 1.4 MYC-m857 89.3 ± 2.5 122.8± 5.1  74.3 ± 1.9 MYC-m867 69.2 ± 2   95.3 ± 4.3 107.5 ± 1.4  MYC-m873  72 ± 1.7 79.5 ± 2.6 104.5 ± 6.6  MYC-m940 92.8 ± 2.1 94.7 ± 4   76.3 ±6.4 MYC-m948 65.4 ± 2.6 76.9 ± 1.7 153.4 ± 11.4 MYC-m956 99.7 ± 3.7121.4 ± 4.8  124.6 ± 3   MYC-m964 139.9 ± 21   158.8 ± 20.7 89.3 ± 2.8MYC-m969 97.7 ± 4.5 135.9 ± 1.3  107.6 ± 6.3  MYC-m980 99.9 ± 3.6 122.7± 4.3  99.1 ± 4.1 MYC-m989   84 ± 8.4 78.3 ± 20  84.2 ± 7.1 MYC-m99466.4 ± 4.3   83 ± 1.3 79.2 ± 4.9 MYC-m1000 89.6 ± 2   90.5 ± 2.9 80.2 ±0.4 MYC-m1006 85.3 ± 3.9 91.7 ± 5.1 90.1 ± 3.4 MYC-m1014 89.7 ± 2.7106.1 ± 4.5  70.4 ± 2.6 MYC-m1020 96.6 ± 1.6 111.9 ± 3.8  75.1 ± 5.2MYC-m1029 105.1 ± 4.1  131.5 ± 7.8  79.5 ± 4.5 MYC-m1046 107.6 ± 4.7 118.2 ± 5.5  77.8 ± 6.3 MYC-m1164 57.9 ± 4   74.3 ± 3.7 105.1 ± 1.5 MYC-m1170 71.1 ± 6.5 69.9 ± 5   80.3 ± 1.4 MYC-m1176 85.2 ± 1.4 81.6 ±1.2 90.8 ± 5.1 MYC-m1258 81.9 ± 2.6   79 ± 2.9 88.4 ± 1.6 MYC-m1269 69.6± 2.6 74.1 ± 3.5 63.5 ± 1.1 MYC-m1391 49.6 ± 1.9 65.1 ± 3.9 100.5 ± 2.2 MYC-m1396 37.7 ± 4.1 68.3 ± 7   67.5 ± 4.1 MYC-m1402 102.4 ± 3.6  126.9± 9.2  93.2 ± 2.7 MYC-m1407 125.1 ± 1.7  136.1 ± 4.3  77.4 ± 6.6MYC-m1414 89.8 ± 6.6 93.4 ± 9.1 90.3 ± 1.9 MYC-m1420 86.3 ± 3.7 82.8 ±3.8 58.5 ± 2.2 MYC-m1426  106 ± 5.4 115.3 ± 2.1  58.5 ± 2.9 MYC-m1431  99 ± 2.4 108.9 ± 2.1  103.9 ± 3   MYC-m1437 102.2 ± 7.2  120.2 ± 8.4 83.5 ± 5.2 MYC-m1443 101.2 ± 3.3  137.3 ± 6.5  82.6 ± 2.2 MYC-m1470 90.8± 3.6 111.5 ± 5.7  84.7 ± 2.2 MYC-m1541   93 ± 3.6 89.5 ± 4.4 82.5 ± 2.7MYC-m1554 102.3 ± 1.6  96.3 ± 4.3 117.3 ± 3.5  MYC-m1614 98.3 ± 2.1 86.4± 2.6 91.7 ± 4.6 MYC-m1619 96.8 ± 4   96.8 ± 7   94.7 ± 3.5 MYC-m162796.1 ± 6.2 98.4 ± 9.3 89.7 ± 4.1 MYC-m1632   91 ± 13.7 104.3 ± 23.2 84.7± 5   MYC-m1638 69.3 ± 4.6 86.7 ± 7.1 75.9 ± 4.4 MYC-m1644 99.1 ± 5.3111.7 ± 8   91.6 ± 5.4 MYC-m1649 112.5 ± 2.6  101.7 ± 6.2  84.2 ± 5.3MYC-m1754 122.1 ± 2.4  101.7 ± 3.8  58.2 ± 1.5 MYC-m1765 101.7 ± 3.7 90.9 ± 3.4 117.2 ± 2.6  MYC-m1778 93.4 ± 3   85.8 ± 2.2 75.2 ± 2  MYC-m1786 93.4 ± 4.6   83 ± 8.6 72.7 ± 3.2 MYC-m1795 70.6 ± 4.7 62.5 ±7.4 152.9 ± 2.9  MYC-m1825 115.5 ± 6.6  161.8 ± 7.5  59.4 ± 1.8MYC-m1838 149.5 ± 2.7  184.3 ± 6.8  103.5 ± 10.7 MYC-m1845 127.6 ± 4.6 232.3 ± 8.5  82.3 ± 2.5 MYC-m1850 106.6 ± 2.7  279.5 ± 8   62.5 ± 0.6MYC-m1855 106.6 ± 7.8  445.6 ± 15.4   88 ± 8.2 MYC-m1860 118.2 ± 5.7  173 ± 6.7 62.6 ± 2.7 MYC-m1873  109 ± 2.4  130 ± 3.9 95.9 ± 8.8MYC-m1879 107.1 ± 5.1  133.6 ± 5.4  79.1 ± 1.2 MYC-m1887 70.4 ± 5.1146.1 ± 6.6   81.3 ± 10.7 MYC-m1896 97.3 ± 3.9 115.3 ± 3.9  74.7 ± 1.7MYC-m1910 95.6 ± 2.5 105.2 ± 2   85.1 ± 7   MYC-m1938 113.4 ± 2.8  116.8± 4   102.5 ± 2   MYC-m1943 99.6 ± 1.7 132.5 ± 5.5  64.9 ± 4.5 MYC-m195189.1 ± 3.8 188.9 ± 5     82 ± 2.4 MYC-m1957 68.4 ± 3.5 215.7 ± 3.1  75.8± 2.3 MYC-m1963 68.9 ± 6.9 123.2 ± 9.3  157.9 ± 3.4  MYC-m1985 75.2 ±1.6  212 ± 4.4 64.8 ± 3.6 MYC-m1995 101.3 ± 4.5  132.7 ± 1.3  58.3 ± 3.5MYC-m2002 136.1 ± 5.6  168.5 ± 11.1 59.2 ± 1.9 MYC-m2011 95.8 ± 5.8166.8 ± 6.8  65.5 ± 2.5 MYC-m2016 109.7 ± 9.1  647.4 ± 6.4  46.1 ± 1.2MYC-m2021 105.8 ± 9   589.1 ± 9.1  67.4 ± 2.4 MYC-m2034 96.9 ± 3.6 238.3± 5     48 ± 1.4 MYC-m2039 96.3 ± 7.6  92.2 ± 12.2 38.1 ± 1.9 MYC-m2044 110 ± 8.2 136 ± 6  55.9 ± 2.3 MYC-m2049 100.9 ± 2.9  107.1 ± 2.9  53.5± 3.5 MYC-m2056 104.2 ± 2.4  116.2 ± 3.6  54.1 ± 2.5 MYC-m2064 94.4 ±3.2 86.5 ± 5.5 43.8 ± 3.6 MYC-m2069 96.6 ± 2.6 79.7 ± 1.2 47.6 ± 4.6MYC-m2096 96.7 ± 3.7 103.6 ± 4.9  59.8 ± 2   MYC-m2103 106.8 ± 2.8 115.6 ± 4.5  51.9 ± 3.8 MYC-m2110 107.8 ±     115.6 ±     39.9 ± 2  MYC-m2117 112.1 ± 2.7  139.1 ± 0.9    49 ± 5.8 MYC-m2125 103.3 ± 2.2 120.6 ± 2.5  46.5 ± 1.9 MYC-m2131   86 ± 3.9   66 ± 15.6 47.7 ± 2.8MYC-m2136 77.4 ± 8.3 68.4 ± 8.8 41.3 ± 1.8 MYC-m2143 76.4 ± 2.2 70.5 ±2.3 70.9 ± 3.1 MYC-m2149 77.6 ± 7.1 78.1 ± 5.2 87.2 ± 3.7 MYC-m2154 75.2± 6.7 80.2 ± 7.2 74.1 ± 4.9 MYC-m2159 88.8 ± 5.3 94.7 ± 7.5 47.8 ± 3.3MYC-m2166   74 ± 4.7 84.2 ± 5.9 48.2 ± 7.2 MYC-m2171 65.1 ± 0.9 59.5 ±2.2 49.1 ± 2.1 MYC-m2177 66.3 ± 4.8   62 ± 4.1 59.4 ± 4   MYC-m2187 41.6± 3.5   35 ± 2.5 65.1 ± 3.3 MYC-m2194 55.7 ± 2.2 54.8 ± 3.1   48 ± 1.5MYC-m2200 83.1 ± 6.2 89.6 ± 4.2 49.9 ± 1.9 MYC-m2208 50.2 ± 2.1 47.6 ±1.6 108.3 ± 6.6  MYC-m2217 68.8 ± 4.8  64.9 ± 10.8 114.8 ± 7.1 MYC-m2224 98.5 ± 7.5  93 ± 10 101.1 ± 4.3  MYC-m2229 110.8 ± 5.6  120.5± 5.9  51.8 ± 8.6 MYC-m2236 107.2 ± 6.1  107.9 ± 6.8  64.6 ± 5  MYC-m2241 101.3 ± 9.3  97.1 ± 7.4 52.2 ± 7.6 MYC-m2255 97.4 ± 1.9 88.8 ±2.7 34.9 ± 9.8 MYC-m2260 128.5 ± 5.3  132.9 ± 6.6   69.4 ± 11.1MYC-m2265 91.9 ± 6   90.8 ± 6.4 57.7 ± 4.7 MYC-m2270  93.6 ± 11.7   93 ±7.1 51.6 ± 3.4 MYC-m2286 97.6 ± 9.9 109.2 ± 8.8  63.6 ± 1.9 MYC-m2291102.8 ± 1.9  105.9 ± 3.7  82.1 ± 8.9 MYC-m2296 93.9 ± 5.8 90.2 ± 8.848.6 ± 3.2 MYC-m2305 112.4 ± 8   111.7 ± 5   84.9 ± 2.1 MYC-m2311  92.3± 10.9  88.8 ± 13.6 59 ± 9 MYC-m2317  65 ± 14  61.4 ± 13.9 63.4 ± 3.2MYC-m2324 59.9 ± 1.7 58.3 ± 4.8  69.4 ± 10.5 MYC-m2333 56.5 ± 3   57.6 ±2.2 89.8 ± 2.9 MYC-m2338 86.2 ± 3.7   97 ± 3.8 92.1 ± 3.6 MYC-m2346104.4 ± 4.7  110.1 ± 3.2  127.3 ± 4.8  MYC-m2351 98.9 ± 5.3 97.4 ± 6.9100.2 ± 5.2  MYC-m2356 103.2 ± 1.6  89.7 ± 2.5 71.2 ± 1.4 MYC-m2362105.9 ± 4.7  85.5 ± 3.9 92.5 ± 2.1 MYC-m2384 140.1 ± 12.4 152.3 ± 14.285.4 ± 6.1 MYC-m2390 122.6 ± 5.6  118.9 ± 8.4  93.9 ± 3.3 MYC-m2397 82.982.9   86 ± 2.6

As shown in above Table 9, 24 of the 327 assayed asymmetric DsiRNAsexamined in human A549 cells reproducibly showed, on average, greaterthan 50% reduction of human MYC levels in A549 cells at 1 nM (MYC-607,MYC-1364, MYC-1370, MYC-1382, MYC-1457, MYC-1465, MYC-1698, MYC-1734,MYC-1769, MYC-1779, MYC-1795, MYC-1808, MYC-1823, MYC-1828, MYC-1845,MYC-1855, MYC-1882, MYC-1911, MYC-1931, MYC-2099, MYC-2120, MYC-2306,MYC-1360 and MYC-1468). Significant variability between assays performedin human cells was observed, with 28 different duplexes showing greaterthan 50% reduction in Myc levels by at least two of three assaysperformed (MYC-1116, MYC-1346, MYC-1351, MYC-1364, MYC-1370, MYC-1382,MYC-1457, MYC-1465, MYC-1584, MYC-1698, MYC-1734, MYC-1769, MYC-1779,MYC-1795, MYC-1808, MYC-1823, MYC-1828, MYC-1845, MYC-1855, MYC-1882,MYC-1911, MYC-1931, MYC-2306, MYC-1360, MYC-1468, MYC-1483, MYC-1711 andMYC-1712). Meanwhile, 47 different duplexes exhibited at least 50%reduction in human Myc levels by only one assay during primaryscreening: MYC-548, MYC-601, MYC-607, MYC-920, MYC-949, MYC-970,MYC-1111, MYC-1340, MYC-1555, MYC-1599, MYC-1639, MYC-1687, MYC-1850,MYC-1893, MYC-1921, MYC-1926, MYC-1944, MYC-1965, MYC-1970, MYC-1976,MYC-1981, MYC-1989, MYC-1994, MYC-2001, MYC-2006, MYC-2013, MYC-2026,MYC-2031, MYC-2040, MYC-2048, MYC-2066, MYC-2073, MYC-2083, MYC-2094,MYC-2099, MYC-2114, MYC-2120, MYC-2176, MYC-2188, MYC-2233, MYC-2300,MYC-622, MYC-952, MYC-953, MYC-1482, MYC-2115 and MYC-2196.

Significant variability between assays performed in mouse cells was alsoobserved, with only three different duplexes showing greater than 50%reduction in Myc levels by at least two of three assays performed(MYC-953, MYC-1360 and MYC-2187). Meanwhile, 23 different duplexesexhibited at least 50% reduction in mouse Myc levels by only one assay:MYC-952, MYC-1468, MYC-m1391, MYC-m1396, MYC-m2016, MYC-m2034,MYC-m2039, MYC-m2064, MYC-m2069, MYC-m2110, MYC-m2117, MYC-m2125,MYC-m2131, MYC-m2136, MYC-m2159, MYC-m2166, MYC-m2171, MYC-m2194,MYC-m2200, MYC-m2208, MYC-m2255 and MYC-m2296.

Assay results of Tables 9 and 10 above were also plotted and are shownin FIGS. 2A to 2H.

Example 3 DsiRNA Inhibition of MYC—Secondary Screen

96 asymmetric DsiRNAs (92 targeting Hs MYC and 4 uniquely targeting MmMYC) of the above experiment were then examined in a secondary assay(“Phase 2”), with results of such assays presented in histogram form inFIGS. 3A to 3H. Specifically, the 96 asymmetric DsiRNAs selected fromthe 327 tested above were assessed for inhibition of human MYC at 1 nMand 0.1 nM in duplicate in the environment of human A549 cells (FIGS. 3Ato 3D). These 96 asymmetric DsiRNAs were also assessed for inhibition ofmouse MYC at 1 nM and 0.1 nM in the environment of mouse Hepa 1-6 cells(FIGS. 3E to 3H). As shown in FIGS. 3A to 3D, a number of asymmetricDsiRNAs reproducibly exhibited significant human MYC inhibitoryefficacies at sub-nanomolar concentrations when assayed in theenvironment of A549 cells. In addition, as shown in FIGS. 3E to 3H, anumber of asymmetric DsiRNAs were identified to possess significantmouse MYC inhibitory efficacies at sub-nanomolar concentrations whenassayed in the environment of mouse Hepa 1-6 cells. (Notably, DsiRNAscapable of significant MYC inhibition in both species, as well asDsiRNAs capable of either human MYC-specific or mouse MYC-specificinhibition were all identified.)

Example 4 Modified Forms of MYC-Targeting DsiRNAs Reduce MYC Levels InVitro

24 MYC-targeting DsiRNAs (MYC-607, MYC-622, MYC-953, MYC-1360, MYC-1364,MYC-1370, MYC-1698, MYC-1711, MYC-1712, MYC-1769, MYC-1926, MYC-1931,MYC-1944, MYC-1965, MYC-1981, MYC-2040, MYC-2066, MYC-2099, MYC-2114,MYC-2115, MYC-2120, MYC-2176, MYC-2196 and MYC-2233) were prepared with2′-O-methyl guide strand modification patterns “M17”, “M35”, “M48” and“M8” as shown above. For each of the 24 DsiRNA sequences, DsiRNAspossessing each of the four guide strand modification patterns M17, M35,M48 and M8 were assayed for MYC inhibition in human A549 cells at 1.0 nMand 0.1 nM (in duplicate) concentrations in the environment of the A549cells. Results of these experiments are presented as histograms in FIGS.4A-4D. These same duplexes were also assayed in mouse Hepa 1-6 cells,with corresponding results shown in FIGS. 4E-4H. In general, the 24DsiRNA sequences exhibited a trend towards reduced efficacy of MYCinhibition as the extent of 2′-O-methyl modification of the guide strandincreased. However, for many of the DsiRNA sequences examined, amodification pattern could be identified that allowed the DsiRNA toretain significant MYC inhibitory efficacy in vitro. It was also notablethat a number of these DsiRNAs (e.g., MYC-1712, MYC-1931, MYC-1944,MYC-1965, MYC-2066, MYC-2114, MYC-2120 and MYC-2233) exhibited noapparent decline in MYC inhibitory efficacy in even the most highlymodified states examined. Thus, such active modified DsiRNA sequencespossess modification patterns believed to be capable of stabilizing suchDsiRNAs and/or reducing immunogenicity of such DsiRNAs whentherapeutically administered to a subject in vivo.

Example 5 Additionally Modified Forms of MYC-Targeting DsiRNAs ReduceMYC Levels In Vitro

19 MYC-targeting DsiRNAs (MYC-622, MYC-953, MYC-1364, MYC-1370,MYC-1698, MYC-1711, MYC-1769, MYC-1926, MYC-1931, MYC-1944, MYC-1965,MYC-2040, MYC-2066, MYC-2099, MYC-2115, MYC-2120, MYC-2176, MYC-2196 andMYC-2233) were prepared with both 2′-O-methyl passenger strand and guidestrand modification patterns. For each of the 19 DsiRNA sequences,DsiRNAs possessing passenger strand modification patterns selected fromSM12, SM14, SM24 and SM31 (referred to as simply “M12”, “M14”, “M24” and“M31” in FIGS. 5A-5F and 6A-6D, where the passenger strand modificationpattern is the first modification pattern listed, followed by the guidestrand modification pattern, e.g., “M12-M48” in FIGS. 5A-5F and 6A-6Dindicates a duplex possessing passenger strand modification pattern“SM12” and guide strand modification pattern “M48”) and guide strandmodification patterns selected from M17, M35, M48 and M8 were assayedfor MYC inhibition in human A549 cells at 1.0 nM and 0.1 nM (induplicate) concentrations in the environment of the A549 cells. Resultsof these experiments are presented as histograms in FIGS. 5A-5F. As inExample 4 above, in general, the 19 DsiRNA sequences exhibited a trendtowards reduced efficacy of MYC inhibition as the extent of 2′-O-methylmodification of both passenger and guide strands increased. However, formany of the DsiRNA sequences examined, a combination of passenger andguide strand modification patterns could be identified that allowed theDsiRNA to retain significant MYC inhibitory efficacy in vitro. It wasalso notable that some of these DsiRNAs (e.g., MYC-1769 and MYC-1965)exhibited no apparent decline in MYC inhibitory efficacy in even themost highly modified states examined. Thus, such active modified DsiRNAsequences possess modification patterns believed to be capable ofstabilizing such DsiRNAs and/or reducing immunogenicity of such DsiRNAswhen therapeutically administered to a subject in vivo.

In certain embodiments, double stranded nucleic acids were selected thattarget the following sequences in MYC mRNA:

TABLE 11 MYC mRNA Target Sequences of Select dsRNAs Human MYC SEQ IDDuplex Name Target mRNA Sequence NO: MYC-607 ACGUUAGCUUCACCAACAGGAACUAUG1977 MYC-622 ACAGGAACUAUGACCUCGACUACGACU 2125 MYC-953GGACGACGAGACCUUCAUCAAAAACAU 2155 MYC-1360 AACAAGAAGAUGAGGAAGAAAUCGAUG2222 MYC-1364 AGAAGAUGAGGAAGAAAUCGAUGUUGU 1996 MYC-1370UGAGGAAGAAAUCGAUGUUGUUUCUGU 1997 MYC-1698 AACGAGCUAAAACGGAGCUUUUUUGCC2022 MYC-1711 GGAGCUUUUUUGCCCUGCGUGACCAGA 2241 MYC-1712GAGCUUUUUUGCCCUGCGUGACCAGAU 2242 MYC-1769 CAAGGUAGUUAUCCUUAAAAAAGCCAC2028 MYC-1926 AGGAAAACGAUUCCUUCUAACAGAAAU 2051 MYC-1931AACGAUUCCUUCUAACAGAAAUGUCCU 2052 MYC-1944 AACAGAAAUGUCCUGAGCAAUCACCUA2054 MYC-1965 CACCUAUGAACUUGUUUCAAAUGCAUG 2057 MYC-1981UCAAAUGCAUGAUCAAAUGCAACCUCA 2060 MYC-2040 UAGCCAUAAUGUAAACUGCCUCAAAUU2069 MYC-2066 UGGACUUUGGGCAUAAAAGAACUUUUU 2073 MYC-2099UACCAUCUUUUUUUUUUCUUUAACAGA 2079 MYC-2114 UUCUUUAACAGAUUUGUAUUUAAGAAU2081 MYC-2115 UCUUUAACAGAUUUGUAUUUAAGAAUU 2254 MYC-2120AACAGAUUUGUAUUUAAGAAUUGUUUU 2082 MYC-2176 CUCUGUAAAUAUUGCCAUUAAAUGUAA2086 MYC-2196 AAUGUAAAUAACUUUAAUAAAACGUUU 2259 MYC-2233CACAGAAUUUCAAUCCUAGUAUAUAGU 2090 MYC-607 ACGUUAGCUUCACCAACAGGA 1323MYC-622 ACAGGAACUAUGACCUCGACU 1471 MYC-953 GGACGACGAGACCUUCAUCAA 1501MYC-1360 AACAAGAAGAUGAGGAAGAAA 1568 MYC-1364 AGAAGAUGAGGAAGAAAUCGA 1342MYC-1370 UGAGGAAGAAAUCGAUGUUGU 1343 MYC-1698 AACGAGCUAAAACGGAGCUUU 1368MYC-1711 GGAGCUUUUUUGCCCUGCGUG 1587 MYC-1712 GAGCUUUUUUGCCCUGCGUGA 1588MYC-1769 CAAGGUAGUUAUCCUUAAAAA 1374 MYC-1926 AGGAAAACGAUUCCUUCUAAC 1397MYC-1931 AACGAUUCCUUCUAACAGAAA 1398 MYC-1944 AACAGAAAUGUCCUGAGCAAU 1400MYC-1965 CACCUAUGAACUUGUUUCAAA 1403 MYC-1981 UCAAAUGCAUGAUCAAAUGCA 1406MYC-2040 UAGCCAUAAUGUAAACUGCCU 1415 MYC-2066 UGGACUUUGGGCAUAAAAGAA 1419MYC-2099 UACCAUCUUUUUUUUUUCUUU 1425 MYC-2114 UUCUUUAACAGAUUUGUAUUU 1427MYC-2115 UCUUUAACAGAUUUGUAUUUA 1600 MYC-2120 AACAGAUUUGUAUUUAAGAAU 1428MYC-2176 CUCUGUAAAUAUUGCCAUUAA 1432 MYC-2196 AAUGUAAAUAACUUUAAUAAA 1605MYC-2233 CACAGAAUUUCAAUCCUAGUA 1436 MYC-607 ACGUUAGCUUCACCAACAG 2958MYC-607 CGUUAGCUUCACCAACAGG 2631 MYC-607 GUUAGCUUCACCAACAGGA 2304MYC-622 ACAGGAACUAUGACCUCGA 3106 MYC-622 CAGGAACUAUGACCUCGAC 2779MYC-622 AGGAACUAUGACCUCGACU 2452 MYC-953 GGACGACGAGACCUUCAUC 3136MYC-953 GACGACGAGACCUUCAUCA 2809 MYC-953 ACGACGAGACCUUCAUCAA 2482MYC-1360 AACAAGAAGAUGAGGAAGA 3203 MYC-1360 ACAAGAAGAUGAGGAAGAA 2876MYC-1360 CAAGAAGAUGAGGAAGAAA 2549 MYC-1364 AGAAGAUGAGGAAGAAAUC 2977MYC-1364 GAAGAUGAGGAAGAAAUCG 2650 MYC-1364 AAGAUGAGGAAGAAAUCGA 2323MYC-1370 UGAGGAAGAAAUCGAUGUU 2978 MYC-1370 GAGGAAGAAAUCGAUGUUG 2651MYC-1370 AGGAAGAAAUCGAUGUUGU 2324 MYC-1698 AACGAGCUAAAACGGAGCU 3003MYC-1698 ACGAGCUAAAACGGAGCUU 2676 MYC-1698 CGAGCUAAAACGGAGCUUU 2349MYC-1711 GGAGCUUUUUUGCCCUGCG 3222 MYC-1711 GAGCUUUUUUGCCCUGCGU 2895MYC-1711 AGCUUUUUUGCCCUGCGUG 2568 MYC-1712 GAGCUUUUUUGCCCUGCGU 3223MYC-1712 AGCUUUUUUGCCCUGCGUG 2896 MYC-1712 GCUUUUUUGCCCUGCGUGA 2569MYC-1769 CAAGGUAGUUAUCCUUAAA 3009 MYC-1769 AAGGUAGUUAUCCUUAAAA 2682MYC-1769 AGGUAGUUAUCCUUAAAAA 2355 MYC-1926 AGGAAAACGAUUCCUUCUA 3032MYC-1926 GGAAAACGAUUCCUUCUAA 2705 MYC-1926 GAAAACGAUUCCUUCUAAC 2378MYC-1931 AACGAUUCCUUCUAACAGA 3033 MYC-1931 ACGAUUCCUUCUAACAGAA 2706MYC-1931 CGAUUCCUUCUAACAGAAA 2379 MYC-1944 AACAGAAAUGUCCUGAGCA 3035MYC-1944 ACAGAAAUGUCCUGAGCAA 2708 MYC-1944 CAGAAAUGUCCUGAGCAAU 2381MYC-1965 CACCUAUGAACUUGUUUCA 3038 MYC-1965 ACCUAUGAACUUGUUUCAA 2711MYC-1965 CCUAUGAACUUGUUUCAAA 2384 MYC-1981 UCAAAUGCAUGAUCAAAUG 3041MYC-1981 CAAAUGCAUGAUCAAAUGC 2714 MYC-1981 AAAUGCAUGAUCAAAUGCA 2387MYC-2040 UAGCCAUAAUGUAAACUGC 3050 MYC-2040 AGCCAUAAUGUAAACUGCC 2723MYC-2040 GCCAUAAUGUAAACUGCCU 2396 MYC-2066 UGGACUUUGGGCAUAAAAG 3054MYC-2066 GGACUUUGGGCAUAAAAGA 2727 MYC-2066 GACUUUGGGCAUAAAAGAA 2400MYC-2099 UACCAUCUUUUUUUUUUCU 3060 MYC-2099 ACCAUCUUUUUUUUUUCUU 2733MYC-2099 CCAUCUUUUUUUUUUCUUU 2406 MYC-2114 UUCUUUAACAGAUUUGUAU 3062MYC-2114 UCUUUAACAGAUUUGUAUU 2735 MYC-2114 CUUUAACAGAUUUGUAUUU 2408MYC-2115 UCUUUAACAGAUUUGUAUU 3235 MYC-2115 CUUUAACAGAUUUGUAUUU 2908MYC-2115 UUUAACAGAUUUGUAUUUA 2581 MYC-2120 AACAGAUUUGUAUUUAAGA 3063MYC-2120 ACAGAUUUGUAUUUAAGAA 2736 MYC-2120 CAGAUUUGUAUUUAAGAAU 2409MYC-2176 CUCUGUAAAUAUUGCCAUU 3067 MYC-2176 UCUGUAAAUAUUGCCAUUA 2740MYC-2176 CUGUAAAUAUUGCCAUUAA 2413 MYC-2196 AAUGUAAAUAACUUUAAUA 3240MYC-2196 AUGUAAAUAACUUUAAUAA 2913 MYC-2196 UGUAAAUAACUUUAAUAAA 2586MYC-2233 CACAGAAUUUCAAUCCUAG 3071 MYC-2233 ACAGAAUUUCAAUCCUAGU 2744MYC-2233 CAGAAUUUCAAUCCUAGUA 2417

Additional select MYC mRNA target sequences include:

TABLE 12 Additional Select MYC mRNA Target Sequences of dsRNAs Human MYCSEQ ID Duplex Name Target mRNA Sequence NO: MYC-607ACGUUAGCUUCACCAACAGGAACUAUG 1977 MYC-622 ACAGGAACUAUGACCUCGACUACGACU2125 MYC-953 GGACGACGAGACCUUCAUCAAAAACAU 2155 MYC-1360AACAAGAAGAUGAGGAAGAAAUCGAUG 2222 MYC-1364 AGAAGAUGAGGAAGAAAUCGAUGUUGU1996 MYC-1370 UGAGGAAGAAAUCGAUGUUGUUUCUGU 1997 MYC-1698AACGAGCUAAAACGGAGCUUUUUUGCC 2022 MYC-1711 GGAGCUUUUUUGCCCUGCGUGACCAGA2241 MYC-1712 GAGCUUUUUUGCCCUGCGUGACCAGAU 2242 MYC-1769CAAGGUAGUUAUCCUUAAAAAAGCCAC 2028 MYC-1926 AGGAAAACGAUUCCUUCUAACAGAAAU2051 MYC-1931 AACGAUUCCUUCUAACAGAAAUGUCCU 2052 MYC-1944AACAGAAAUGUCCUGAGCAAUCACCUA 2054 MYC-1965 CACCUAUGAACUUGUUUCAAAUGCAUG2057 MYC-1981 UCAAAUGCAUGAUCAAAUGCAACCUCA 2060 MYC-2040UAGCCAUAAUGUAAACUGCCUCAAAUU 2069 MYC-2066 UGGACUUUGGGCAUAAAAGAACUUUUU2073 MYC-2099 UACCAUCUUUUUUUUUUCUUUAACAGA 2079 MYC-2114UUCUUUAACAGAUUUGUAUUUAAGAAU 2081 MYC-2115 UCUUUAACAGAUUUGUAUUUAAGAAUU2254 MYC-2120 AACAGAUUUGUAUUUAAGAAUUGUUUU 2082 MYC-2176CUCUGUAAAUAUUGCCAUUAAAUGUAA 2086 MYC-2196 AAUGUAAAUAACUUUAAUAAAACGUUU2259 MYC-2233 CACAGAAUUUCAAUCCUAGUAUAUAGU 2090 MYC-1360AACAAGAAGAUGAGGAAGAAA 1568 MYC-1364 AGAAGAUGAGGAAGAAAUCGA 1342 MYC-1370UGAGGAAGAAAUCGAUGUUGU 1343 MYC-1698 AACGAGCUAAAACGGAGCUUU 1368 MYC-1769CAAGGUAGUUAUCCUUAAAAA 1374 MYC-1931 AACGAUUCCUUCUAACAGAAA 1398 MYC-1944AACAGAAAUGUCCUGAGCAAU 1400 MYC-1965 CACCUAUGAACUUGUUUCAAA 1403 MYC-1981UCAAAUGCAUGAUCAAAUGCA 1406 MYC-2040 UAGCCAUAAUGUAAACUGCCU 1415 MYC-2066UGGACUUUGGGCAUAAAAGAA 1419 MYC-2099 UACCAUCUUUUUUUUUUCUUU 1425 MYC-2114UUCUUUAACAGAUUUGUAUUU 1427 MYC-2115 UCUUUAACAGAUUUGUAUUUA 1600 MYC-2176CUCUGUAAAUAUUGCCAUUAA 1432 MYC-2196 AAUGUAAAUAACUUUAAUAAA 1605 MYC-2233CACAGAAUUUCAAUCCUAGUA 1436 MYC-1360 AACAAGAAGAUGAGGAAGA 3203 MYC-1360ACAAGAAGAUGAGGAAGAA 2876 MYC-1360 CAAGAAGAUGAGGAAGAAA 2549 MYC-1364AGAAGAUGAGGAAGAAAUC 2977 MYC-1364 GAAGAUGAGGAAGAAAUCG 2650 MYC-1364AAGAUGAGGAAGAAAUCGA 2323 MYC-1370 UGAGGAAGAAAUCGAUGUU 2978 MYC-1370GAGGAAGAAAUCGAUGUUG 2651 MYC-1370 AGGAAGAAAUCGAUGUUGU 2324 MYC-1698AACGAGCUAAAACGGAGCU 3003 MYC-1698 ACGAGCUAAAACGGAGCUU 2676 MYC-1698CGAGCUAAAACGGAGCUUU 2349 MYC-1769 CAAGGUAGUUAUCCUUAAA 3009 MYC-1769AAGGUAGUUAUCCUUAAAA 2682 MYC-1769 AGGUAGUUAUCCUUAAAAA 2355 MYC-1931AACGAUUCCUUCUAACAGA 3033 MYC-1931 ACGAUUCCUUCUAACAGAA 2706 MYC-1931CGAUUCCUUCUAACAGAAA 2379 MYC-1944 AACAGAAAUGUCCUGAGCA 3035 MYC-1944ACAGAAAUGUCCUGAGCAA 2708 MYC-1944 CAGAAAUGUCCUGAGCAAU 2381 MYC-1965CACCUAUGAACUUGUUUCA 3038 MYC-1965 ACCUAUGAACUUGUUUCAA 2711 MYC-1965CCUAUGAACUUGUUUCAAA 2384 MYC-1981 UCAAAUGCAUGAUCAAAUG 3041 MYC-1981CAAAUGCAUGAUCAAAUGC 2714 MYC-1981 AAAUGCAUGAUCAAAUGCA 2387 MYC-2040UAGCCAUAAUGUAAACUGC 3050 MYC-2040 AGCCAUAAUGUAAACUGCC 2723 MYC-2040GCCAUAAUGUAAACUGCCU 2396 MYC-2066 UGGACUUUGGGCAUAAAAG 3054 MYC-2066GGACUUUGGGCAUAAAAGA 2727 MYC-2066 GACUUUGGGCAUAAAAGAA 2400 MYC-2099UACCAUCUUUUUUUUUUCU 3060 MYC-2099 ACCAUCUUUUUUUUUUCUU 2733 MYC-2099CCAUCUUUUUUUUUUCUUU 2406 MYC-2114 UUCUUUAACAGAUUUGUAU 3062 MYC-2114UCUUUAACAGAUUUGUAUU 2735 MYC-2114 CUUUAACAGAUUUGUAUUU 2408 MYC-2115UCUUUAACAGAUUUGUAUU 3235 MYC-2115 CUUUAACAGAUUUGUAUUU 2908 MYC-2115UUUAACAGAUUUGUAUUUA 2581 MYC-2176 CUCUGUAAAUAUUGCCAUU 3067 MYC-2176UCUGUAAAUAUUGCCAUUA 2740 MYC-2176 CUGUAAAUAUUGCCAUUAA 2413 MYC-2196AAUGUAAAUAACUUUAAUA 3240 MYC-2196 AUGUAAAUAACUUUAAUAA 2913 MYC-2196UGUAAAUAACUUUAAUAAA 2586 MYC-2233 CACAGAAUUUCAAUCCUAG 3071 MYC-2233ACAGAAUUUCAAUCCUAGU 2744 MYC-2233 CAGAAUUUCAAUCCUAGUA 2417

Further select MYC mRNA target sequences include:

TABLE 13 Further Select MYC mRNA Target Sequences of dsRNAs Human MYCSEQ ID Duplex Name Target mRNA Sequence NO: MYC-607ACGUUAGCUUCACCAACAGGAACUAUG 1977 MYC-953 GGACGACGAGACCUUCAUCAAAAACAU2155 MYC-1364 AGAAGAUGAGGAAGAAAUCGAUGUUGU 1996 MYC-1370UGAGGAAGAAAUCGAUGUUGUUUCUGU 1997 MYC-1698 AACGAGCUAAAACGGAGCUUUUUUGCC2022 MYC-1711 GGAGCUUUUUUGCCCUGCGUGACCAGA 2241 MYC-1712GAGCUUUUUUGCCCUGCGUGACCAGAU 2242 MYC-1769 CAAGGUAGUUAUCCUUAAAAAAGCCAC2028 MYC-1926 AGGAAAACGAUUCCUUCUAACAGAAAU 2051 MYC-1931AACGAUUCCUUCUAACAGAAAUGUCCU 2052 MYC-1944 AACAGAAAUGUCCUGAGCAAUCACCUA2054 MYC-1981 UCAAAUGCAUGAUCAAAUGCAACCUCA 2060 MYC-2040UAGCCAUAAUGUAAACUGCCUCAAAUU 2069 MYC-2066 UGGACUUUGGGCAUAAAAGAACUUUUU2073 MYC-2099 UACCAUCUUUUUUUUUUCUUUAACAGA 2079 MYC-2114UUCUUUAACAGAUUUGUAUUUAAGAAU 2081 MYC-2115 UCUUUAACAGAUUUGUAUUUAAGAAUU2254 MYC-2120 AACAGAUUUGUAUUUAAGAAUUGUUUU 2082 MYC-2176CUCUGUAAAUAUUGCCAUUAAAUGUAA 2086 MYC-2196 AAUGUAAAUAACUUUAAUAAAACGUUU2259 MYC-2233 CACAGAAUUUCAAUCCUAGUAUAUAGU 2090 MYC-607ACGUUAGCUUCACCAACAGGA 1323 MYC-953 GGACGACGAGACCUUCAUCAA 1501 MYC-1364AGAAGAUGAGGAAGAAAUCGA 1342 MYC-1370 UGAGGAAGAAAUCGAUGUUGU 1343 MYC-1698AACGAGCUAAAACGGAGCUUU 1368 MYC-1711 GGAGCUUUUUUGCCCUGCGUG 1587 MYC-1712GAGCUUUUUUGCCCUGCGUGA 1588 MYC-1769 CAAGGUAGUUAUCCUUAAAAA 1374 MYC-1926AGGAAAACGAUUCCUUCUAAC 1397 MYC-1931 AACGAUUCCUUCUAACAGAAA 1398 MYC-1944AACAGAAAUGUCCUGAGCAAU 1400 MYC-1981 UCAAAUGCAUGAUCAAAUGCA 1406 MYC-2040UAGCCAUAAUGUAAACUGCCU 1415 MYC-2066 UGGACUUUGGGCAUAAAAGAA 1419 MYC-2099UACCAUCUUUUUUUUUUCUUU 1425 MYC-2114 UUCUUUAACAGAUUUGUAUUU 1427 MYC-2115UCUUUAACAGAUUUGUAUUUA 1600 MYC-2120 AACAGAUUUGUAUUUAAGAAU 1428 MYC-2176CUCUGUAAAUAUUGCCAUUAA 1432 MYC-2196 AAUGUAAAUAACUUUAAUAAA 1605 MYC-2233CACAGAAUUUCAAUCCUAGUA 1436 MYC-607 ACGUUAGCUUCACCAACAG 2958 MYC-607CGUUAGCUUCACCAACAGG 2631 MYC-607 GUUAGCUUCACCAACAGGA 2304 MYC-953GGACGACGAGACCUUCAUC 3136 MYC-953 GACGACGAGACCUUCAUCA 2809 MYC-953ACGACGAGACCUUCAUCAA 2482 MYC-1364 AGAAGAUGAGGAAGAAAUC 2977 MYC-1364GAAGAUGAGGAAGAAAUCG 2650 MYC-1364 AAGAUGAGGAAGAAAUCGA 2323 MYC-1370UGAGGAAGAAAUCGAUGUU 2978 MYC-1370 GAGGAAGAAAUCGAUGUUG 2651 MYC-1370AGGAAGAAAUCGAUGUUGU 2324 MYC-1698 AACGAGCUAAAACGGAGCU 3003 MYC-1698ACGAGCUAAAACGGAGCUU 2676 MYC-1698 CGAGCUAAAACGGAGCUUU 2349 MYC-1711GGAGCUUUUUUGCCCUGCG 3222 MYC-1711 GAGCUUUUUUGCCCUGCGU 2895 MYC-1711AGCUUUUUUGCCCUGCGUG 2568 MYC-1712 GAGCUUUUUUGCCCUGCGU 3223 MYC-1712AGCUUUUUUGCCCUGCGUG 2896 MYC-1712 GCUUUUUUGCCCUGCGUGA 2569 MYC-1769CAAGGUAGUUAUCCUUAAA 3009 MYC-1769 AAGGUAGUUAUCCUUAAAA 2682 MYC-1769AGGUAGUUAUCCUUAAAAA 2355 MYC-1926 AGGAAAACGAUUCCUUCUA 3032 MYC-1926GGAAAACGAUUCCUUCUAA 2705 MYC-1926 GAAAACGAUUCCUUCUAAC 2378 MYC-1931AACGAUUCCUUCUAACAGA 3033 MYC-1931 ACGAUUCCUUCUAACAGAA 2706 MYC-1931CGAUUCCUUCUAACAGAAA 2379 MYC-1944 AACAGAAAUGUCCUGAGCA 3035 MYC-1944ACAGAAAUGUCCUGAGCAA 2708 MYC-1944 CAGAAAUGUCCUGAGCAAU 2381 MYC-1981UCAAAUGCAUGAUCAAAUG 3041 MYC-1981 CAAAUGCAUGAUCAAAUGC 2714 MYC-1981AAAUGCAUGAUCAAAUGCA 2387 MYC-2040 UAGCCAUAAUGUAAACUGC 3050 MYC-2040AGCCAUAAUGUAAACUGCC 2723 MYC-2040 GCCAUAAUGUAAACUGCCU 2396 MYC-2066UGGACUUUGGGCAUAAAAG 3054 MYC-2066 GGACUUUGGGCAUAAAAGA 2727 MYC-2066GACUUUGGGCAUAAAAGAA 2400 MYC-2099 UACCAUCUUUUUUUUUUCU 3060 MYC-2099ACCAUCUUUUUUUUUUCUU 2733 MYC-2099 CCAUCUUUUUUUUUUCUUU 2406 MYC-2114UUCUUUAACAGAUUUGUAU 3062 MYC-2114 UCUUUAACAGAUUUGUAUU 2735 MYC-2114CUUUAACAGAUUUGUAUUU 2408 MYC-2115 UCUUUAACAGAUUUGUAUU 3235 MYC-2115CUUUAACAGAUUUGUAUUU 2908 MYC-2115 UUUAACAGAUUUGUAUUUA 2581 MYC-2120AACAGAUUUGUAUUUAAGA 3063 MYC-2120 ACAGAUUUGUAUUUAAGAA 2736 MYC-2120CAGAUUUGUAUUUAAGAAU 2409 MYC-2176 CUCUGUAAAUAUUGCCAUU 3067 MYC-2176UCUGUAAAUAUUGCCAUUA 2740 MYC-2176 CUGUAAAUAUUGCCAUUAA 2413 MYC-2196AAUGUAAAUAACUUUAAUA 3240 MYC-2196 AUGUAAAUAACUUUAAUAA 2913 MYC-2196UGUAAAUAACUUUAAUAAA 2586 MYC-2233 CACAGAAUUUCAAUCCUAG 3071 MYC-2233ACAGAAUUUCAAUCCUAGU 2744 MYC-2233 CAGAAUUUCAAUCCUAGUA 2417

Certain additional selections of MYC mRNA targets included thefollowing:

TABLE 14 Selected MYC mRNA Target Sequences of dsRNAs Human MYC SEQ IDDuplex Name Target mRNA Sequence NO: MYC-2099UACCAUCUUUUUUUUUUCUUUAACAGA 2079 MYC-2176 CUCUGUAAAUAUUGCCAUUAAAUGUAA2086 MYC-2196 AAUGUAAAUAACUUUAAUAAAACGUUU 2259 MYC-1698AACGAGCUAAAACGGAGCUUU 1368 MYC-1769 CAAGGUAGUUAUCCUUAAAAA 1374 MYC-1931AACGAUUCCUUCUAACAGAAA 1398 MYC-1944 AACAGAAAUGUCCUGAGCAAU 1400 MYC-1981UCAAAUGCAUGAUCAAAUGCA 1406 MYC-2099 UACCAUCUUUUUUUUUUCUUU 1425 MYC-2176CUCUGUAAAUAUUGCCAUUAA 1432 MYC-2196 AAUGUAAAUAACUUUAAUAAA 1605 MYC-2233CACAGAAUUUCAAUCCUAGUA 1436 MYC-1698 AACGAGCUAAAACGGAGCU 3003 MYC-1698ACGAGCUAAAACGGAGCUU 2676 MYC-1698 CGAGCUAAAACGGAGCUUU 2349 MYC-1769CAAGGUAGUUAUCCUUAAA 3009 MYC-1769 AAGGUAGUUAUCCUUAAAA 2682 MYC-1769AGGUAGUUAUCCUUAAAAA 2355 MYC-1931 AACGAUUCCUUCUAACAGA 3033 MYC-1931ACGAUUCCUUCUAACAGAA 2706 MYC-1931 CGAUUCCUUCUAACAGAAA 2379 MYC-1944AACAGAAAUGUCCUGAGCA 3035 MYC-1944 ACAGAAAUGUCCUGAGCAA 2708 MYC-1944CAGAAAUGUCCUGAGCAAU 2381 MYC-1981 UCAAAUGCAUGAUCAAAUG 3041 MYC-1981CAAAUGCAUGAUCAAAUGC 2714 MYC-1981 AAAUGCAUGAUCAAAUGCA 2387 MYC-2066UGGACUUUGGGCAUAAAAG 3054 MYC-2066 GGACUUUGGGCAUAAAAGA 2727 MYC-2099UACCAUCUUUUUUUUUUCU 3060 MYC-2099 ACCAUCUUUUUUUUUUCUU 2733 MYC-2099CCAUCUUUUUUUUUUCUUU 2406 MYC-2114 UUCUUUAACAGAUUUGUAU 3062 MYC-2114UCUUUAACAGAUUUGUAUU 2735 MYC-2115 UCUUUAACAGAUUUGUAUU 3235 MYC-2176CUCUGUAAAUAUUGCCAUU 3067 MYC-2176 UCUGUAAAUAUUGCCAUUA 2740 MYC-2176CUGUAAAUAUUGCCAUUAA 2413 MYC-2196 AAUGUAAAUAACUUUAAUA 3240 MYC-2196AUGUAAAUAACUUUAAUAA 2913 MYC-2196 UGUAAAUAACUUUAAUAAA 2586 MYC-2233CACAGAAUUUCAAUCCUAG 3071 MYC-2233 ACAGAAUUUCAAUCCUAGU 2744 MYC-2233CAGAAUUUCAAUCCUAGUA 2417

Certain further selections of MYC mRNA targets included the following:

TABLE 15 Further Selected MYC mRNA Target Sequences of dsRNAs Human MYCSEQ ID Duplex Name Target mRNA Sequence NO: MYC-2176CUCUGUAAAUAUUGCCAUUAAAUGUAA 2086 MYC-2099 UACCAUCUUUUUUUUUUCUUU 1425MYC-2176 CUCUGUAAAUAUUGCCAUUAA 1432 MYC-2196 AAUGUAAAUAACUUUAAUAAA 1605MYC-1769 AGGUAGUUAUCCUUAAAAA 2355 MYC-2099 UACCAUCUUUUUUUUUUCU 3060MYC-2099 ACCAUCUUUUUUUUUUCUU 2733 MYC-2099 CCAUCUUUUUUUUUUCUUU 2406MYC-2176 CUCUGUAAAUAUUGCCAUU 3067 MYC-2176 UCUGUAAAUAUUGCCAUUA 2740MYC-2176 CUGUAAAUAUUGCCAUUAA 2413 MYC-2196 AAUGUAAAUAACUUUAAUA 3240MYC-2196 AUGUAAAUAACUUUAAUAA 2913 MYC-2196 UGUAAAUAACUUUAAUAAA 2586

Example 6 Target mRNA Mismatch Tolerance of MYC-Targeting DsiRNAs

Whether seven different native MYC mRNA-targeting DsiRNAs (MYC-622,MYC-953, MYC-1364, MYC-1370, MYC-1711, MYC-1769 and MYC-1965) couldincorporate mismatches with respect to their target mRNA sequence yetstill retain robust inhibitory activity was examined. As shown in FIGS.6A-6D, the following DsiRNA duplex sequences (possessing passengerstrand-guide strand modification patterns as indicated) were tested forMYC knockdown activity (Bold indicates residues that form mismatcheswith respect to the target MYC transcript sequence):

MYC-622 (Native sequence): (SEQ ID NO: 163)5′-AGGAACUAUGACCUCGACUACGAct-3′ (SEQ ID NO: 490)3′-UGUCCUUGAUACUGGAGCUGAUGCUGA-5′ MYC-622_m1: (SEQ ID NO: 3879)5′-AGGAACCAUGACCUCGACUACGAct-3′ (SEQ ID NO: 3880)3′-UGUCCUUGGUACUGGAGCUGAUGCUGA-5′ MYC-622_m2: (SEQ ID NO: 3881)5′-AGAAACUAUGACCUCGACUACAAct-3′ (SEQ ID NO: 3882)3′-UGUCUUUGAUACUGGAGCUGAUGUUGA-5′ MYC-622_m3: (SEQ ID NO: 3883)5′-AAGAACUAUGACCUCGACUAACGct-3′ (SEQ ID NO: 3884)3′-UGUUCUUGAUACUGGAGCUGAUUGCGA-5′ MYC-953 (Native sequence): (SEQ ID NO:193) 5′-ACGACGAGACCUUCAUCAAAAACat-3′ (SEQ ID NO: 520)3′-CCUGCUGCUCUGGAAGUAGUUUUUGUA-5′ MYC-953_m1: (SEQ ID NO: 3885)5′-ACAACGAGACCUUCAUCAAAAACat-3′ (SEQ ID NO: 3886)3′-CCUGUUGCUCUGGAAGUAGUUUUUGUA-5′ MYC-953_m2: (SEQ ID NO: 3887)5′-ACGACAAGACCUUCAUCAAAAACat-3′ (SEQ ID NO: 3888)3′-CCUGCUGUUCUGGAAGUAGUUUUUGUA-5′ MYC-953_m3: (SEQ ID NO: 3889)5′-ACGACGAGACCUUCAUCAAUAACat-3′ (SEQ ID NO: 3890)3′-UCUGCUGCUCUGGAAGUAGUUAUUGUA-5′ MYC-1364 (Native sequence): (SEQ IDNO: 34) 5′-AAGAUGAGGAAGAAAUCGAUGUUgt-3′ (SEQ ID NO: 361)3′-UCUUCUACUCCUUCUUUAGCUACAACA-5′ MYC-1364_m1: (SEQ ID NO: 3891)5′-AAGAUGAAGAAGAAAUCGAUGUUgt-3′ (SEQ ID NO: 3892)3′-UCUUCUACUUCUUCUUUAGCUACAACA-5′ MYC-1364_m2: (SEQ ID NO: 3893)5′-AAGAUGAGGAAGAAAUCGAAGUUgt-3′ (SEQ ID NO: 3894)3′-UCUUCUACUCCUUCUUUAGCUUCAACA-5′ MYC-1364_m3: (SEQ ID NO: 3895)5′-AAGAUGAGGAAGAAAUCGAUGAUgt-3′ (SEQ ID NO: 3896)3′-UCUUCUACUCCUUCUUUAGCUACUACA-5′ MYC-1364_m4: (SEQ ID NO: 3897)5′-AAGAUGAGGAAGAAAUCGAUAGUgt-3′ (SEQ ID NO: 3898)3′-UCUUCUACUCCUUCUUUAGCUAUCACA-5′ MYC-1370 (Native sequence): (SEQ IDNO: 35) 5′-AGGAAGAAAUCGAUGUUGUUUCUgt-3′ (SEQ ID NO: 362)3′-ACUCCUUCUUUAGCUACAACAAAGACA-5′ MYC-1370_m1: (SEQ ID NO: 3899)5′-AAGAAGAAAUCGAUGUUGUUACUgt-3′ (SEQ ID NO: 3900)3′-ACUUCUUCUUUAGCUACAACAAUGACA-5′ MYC-1370_m2: (SEQ ID NO: 3901)5′-AGAAAGAAAUCGAUGUUGUUACUgt-3′ (SEQ ID NO: 3902)3′-ACUCUUUCUUUAGCUACAACAAUGACA-5′ MYC-1370_m3: (SEQ ID NO: 3903)5′-AGGAAAAAAUCGAUGUUGUUACUgt-3′ (SEQ ID NO: 3904)3′-ACUCCUUUUUUAGCUACAACAAUGACA-5′ MYC-1370_m4: (SEQ ID NO: 3905)5′-AGGAAAAAAUCGAUGUUGUUUUCgt-3′ (SEQ ID NO: 3906)3′-ACUCCUUUUUUAGCUACAACAAAAGCA-5′ MYC-1711 (Native sequence): (SEQ IDNO: 279) 5′-AGCUUUUUUGCCCUGCGUGACCAga-3′ (SEQ ID NO: 606)3′-CCUCGAAAAAACGGGACGCACUGGUCU-5′ MYC-1711_m1: (SEQ ID NO: 3907)5′-AGCUUUCUUGCCCUGCGUGACCAga-3′ (SEQ ID NO: 3908)3′-CCUCGAAAGAACGGGACGCACUGGUCU-5′ MYC-1711_m3: (SEQ ID NO: 3909)5′-AGCUUCUUUGCCCUGCGUGAACCga-3′ (SEQ ID NO: 3910)3′-CCUCGAAGAAACGGGACGCACUUGGCU-5′ MYC-1711_m4: (SEQ ID NO: 3911)5′-AGCUCUUUUGCCCUGCGUGUCCAga-3′ (SEQ ID NO: 3912)3′-CCUCGAGAAAACGGGACGCACAGGUCU-5′ MYC-1769 (Native sequence): (SEQ IDNO: 66) 5′-AGGUAGUUAUCCUUAAAAAAGCCac-3′ (SEQ ID NO: 393)3′-GUUCCAUCAAUAGGAAUUUUUUCGGUG-5′ MYC-1769_m1: (SEQ ID NO: 3913)5′-AGGUAGUUAUCCUUAAAAAACCCac-3′ (SEQ ID NO: 3914)3′-GUUCCAUCAAUAGGAAUUUUUUGGGUG-5′ MYC-1769_m2: (SEQ ID NO: 3915)5′-AGGUAGUUAUCCUUAAAAAAGGCac-3′ (SEQ ID NO: 3916)3′-GUUCCAUCAAUAGGAAUUUUUUCCGUG-5′ MYC-1769_m4: (SEQ ID NO: 3917)5′-AGGUAGUUAUCCUUAAAAAAAGCcc-3′ (SEQ ID NO: 3918)3′-GUUCCAUCAAUAGGAAUUUUUUUCGGG-5′ MYC-1769_m5: (SEQ ID NO: 3919)5′-AGGCAGUUAUCCUUAAAAAAGCCac-3′ (SEQ ID NO: 3920)3′-GUUCCGUCAAUAGGAAUUUUUUCGGUG-5′ MYC-1965 (Native sequence): (SEQ IDNO: 95) 5′-CCUAUGAACUUGUUUCAAAUGCAtg-3′ (SEQ ID NO: 422)3′-GUGGAUACUUGAACAAAGUUUACGUAC-5′ MYC-1965_m1: (SEQ ID NO: 3921)5′-CCUAUAAACUUGUUUCAAAUGCAtg-3′ (SEQ ID NO: 3922)3′-GUGGAUAUUUGAACAAAGUUUACGUAC-5′ MYC-1965_m2: (SEQ ID NO: 3923)5′-CCUAUGAACUUGUUUCAAAUGCUtg-3′ (SEQ ID NO: 3924)3′-CUGGAUACUUGAACAAAGUUUACGAAC-5′ MYC-1965_m3: (SEQ ID NO: 3925)5′-CCUAUGAACUUGUUUCAAAUGCAag-3′ (SEQ ID NO: 3926)3′-CUGGAUACUUGAACAAAGUUUACGUUC-5′ MYC-1965_m4: (SEQ ID NO: 3927)5′-CCUAUGAACUUGUUUCAAAUAGCtg-3′ (SEQ ID NO: 3928)3′-CUGGAUACUUGAACAAAGUUUAUCGAC-5′As shown in FIGS. 6A-6D, most of the above duplexes possessingmismatches with respect to target MYC transcript sequences retained MYCknockdown activity. For many, the potency of such knockdown was similarto that observed for native duplex sequences.

Example 7 Further Modification Pattern Assessment of MYC-TargetingDsiRNAs In Vitro

Three MYC-targeting duplex sequences (MYC-622, MYC-953 and MYC-1711)were further examined for robustness of anti-MYC activity whilepossessing varying modifications of both sense and antisense strands (asdescribed above, also see FIGS. 7A to 7H for schematics of duplexmodification patterns used, and FIGS. 71 and 7J for schematics ofindividual sense and antisense strand modification patterns,respectively). As shown in FIGS. 7K and 7L, a number of highly modifiedforms of each of the MYC-622, MYC-953 and MYC 1711 duplexes wereidentified to possess robust inhibitory activity, with many suchnewly-tested modified duplexes improving upon the level of activityobserved for M12-M48-modified duplexes in “Phase 5” (described above).Thus, many highly modified and robustly active MYC duplexes wereidentified.

Example 8 In Vivo Efficacy of MYC-Targeting DsiRNAs

The ability of certain, active MYC-targeting DsiRNAs to reduce tumorburden within two orthotopic models of human hepatocellular carcinoma(HCC), Hep3B and HepG2, was examined. To perform such experiments, malenude mice were orthotopically implanted with 2×10⁶ Hep3B cells (ATCC) in50% Matrigel. On day 12 post-implant, serum was collected for humanalpha-fetoprotein (AFP) analysis (human AFP is a serum marker indicativeof the establishment and progression of HCC tumors, e.g., Hep3B andHepG2 tumors). Animals were randomized and assigned to groups based onAFP levels (n=7/group). Dosing of animals with lipid nanoparticles(LNPs) containing DsiRNAs (here, an LNP formulation named EnCore-2072was employed) was initiated on day 13 Animals were dosed at 5 mg/kg iv,tiw×2 (6 doses total). Animals were sacrificed on 48 hrs after the lastdose (day 27 post implant). Tumors were dissected from the liver andweighed. As shown in FIG. 8, all MYC-targeting DsiRNAs examined showedsignificant tumor reduction as compared to untreated subjects.Specifically, indicated modified forms of all tested MYC-targetingDsiRNAs MYC-622, MYC-953, MYC-1364, MYC-1370, MYC-1711 and MYC-1769exhibited tumor inhibition magnitudes of between 61% and 81% as comparedto PBS-treated control subjects. Consistent with these levels of Hep3Btumor reduction, a reduction in AFP levels was also observed (data notshown). Notably, DsiRNAs targeting both human and mouse MYC and DsiRNAstargeting only human MYC showed effective reduction of tumor levels,confirming that the observed effect was attributable to DsiRNA-mediatedtargeting of human MYC.

The ability of MYC-targeting DsiRNAs to reduce tumor burden in a HepG2model of HCC was also examined. In these experiments, male nude micewere orthotopically implanted with 3×106 HepG2 cells (ATCC) in 50%Matrigel. On day 12 post implant, serum was collected for AFP analysis.Animals were randomized and assigned to groups based on AFP levels(n=15/group). Dosing of animals with lipid nanoparticles (LNPs)containing DsiRNAs (here, an LNP formulation named EnCore-2072 wasemployed) was initiated on day 13. Animals were dosed at 5 mg/kg iv,tiw×2 (7 doses total) Animals were sacrificed on 48 hrs after the lastdose (day 29 post implant). Tumors were dissected from the liver andweighed. As shown in FIG. 9, significant reduction of HepG2 tumor burdenwas observed in mice administered either a β-catenin-targeting DsiRNA(HepG2 is known to be β-catenin-dependent) or a MYC-622 DsiRNA. Here,the extent of tumor reduction was compared to a DsiRNA targeting theHPRT1 housekeeping gene, with such comparison indicating a significant,39% reduction of tumor burden in MYC-622 DsiRNA-treated mice. Suchreduction in tumor levels again correlated with an observed reduction inAFP levels (data not shown).

Thus, treatment of established tumors with MYC-targeting DsiRNAs reducedtumor burden and AFP levels in two different models of liver cancer(here, Hep3B and HepG2 tumors were used as art-recognized models ofhuman HCC).

The in vivo knockdown efficacy of MYC-1711 duplexes was further exploredfor dose-dependence. In such experiments, mice bearing Hep3B orthotopicliver tumors were dosed intravenously with PBS, or with MYC-1711-M12/M48DsiRNA formulated in a lipid nanoparticle (LNP2141) at doses of 1, 3, 5,10 and 15 mg/kg. Two days later, mice were sacrificed and tumor RNA wasisolated and analyzed by qPCR. As shown in FIG. 10, MYC mRNA expressionwas effectively knocked down at all doses, with extent of observedknockdown ranging from approximately 50% at the 1 mg/kg dose toapproximately 75% or more at all doses at or above 5 mg/kg. Thus, invivo dose-dependence of MYC mRNA knockdown was demonstrated for theMYC-1711 duplex.

Duration of MYC-targeting DsiRNA in vivo knockdown of MYC expression wasalso assessed in mice bearing Hep3B orthotopic liver tumors. Such micewere dosed intravenously with PBS, or with MYC-1711-M12/M48 DsiRNAformulated in a lipid nanoparticle (LNP2141) at doses of 1 and 5 mg/kg.At time points of 48 h, 96 h and 168 h after the single dose, mice weresacrificed and tumor RNA was isolated and analyzed by qPCR. MYC mRNAexpression was effectively knocked down for multiple days at both 1mg/kg and 5 mg/kg doses of the MYC-1711 duplex, with 1 mg/kg dosesexhibiting approximately 40% reduction of MYC mRNA levels at 2 days and4 days, while 5 mg/kg doses exhibited approximately 60% reduction,approximately 50% reduction and approximately 40% reduction of MYC mRNAlevels at 2 days, 4 days and 168 h, respectively. Thus, MYC-1711duplexes showed durable knockdown effects in vivo, and the persistenceof such effects was also dose-dependent.

In additional experiments, dose-dependence of treatment of Hep3B tumorswas observed while progressing from 0.5 mg/kg to 1 mg/kg to 2 mg/kg to 5mg/kg levels of DsiRNA formulations (FIG. 12). Specifically, micebearing Hep3B orthotopic liver tumors were dosed intravenously with PBS,or HPRT1-716-M21/M36 or MYC-1711-M12/M48 DsiRNAs formulated in a lipidnanoparticle (LNP2141), at three-times-a-week doses of 0.5 mg/kg, 1mg/kg, 2 mg/kg or 5 mg/kg (TIW, 7 total dosings), or at 1 mg/kgtwice-a-week (BIW, six total). Forty-eight hours after the final dose,mice were sacrificed and tumors were weighed. As shown in FIG. 12, tumorgrowth was significantly inhibited by MYC-1711 DsiRNA at all doses, butnot by the HPRT1 DsiRNA. Specifically, 0.5 mg/kg TIW MYC-1711 (M12/M48)was observed to have decreased tumor weight by approximately 35-40%, 1mg/kg TIW MYC-1711 (M12/M48) was observed to have decreased tumor weightby approximately 55%, 3 mg/kg TIW MYC-1711 (M12/M48) was observed tohave decreased tumor weight by approximately 60%, 5 mg/kg TIW MYC-1711(M12/M48) was observed to have decreased tumor weight by approximately75-80% and 1 mg/kg BIW MYC-1711 (M12/M48) was observed to have decreasedtumor weight by approximately 55% on average. Thus, anti-tumor efficacyof MYC-targeting duplexes in reducing tumor weight in an in vivo Hep3Borthotopic liver model was observed to be both significant anddose-dependent.

The MYC-1711 duplex was tested for the ability to harbor extensive2′O-methylation while still retaining MYC knockdown efficacy and/ortumor reduction in vivo. Mice bearing Hep3B orthotopic liver tumors weredosed intravenously with PBS, or with the following MYC-1711 DsiRNAsformulated in lipid nanoparticle (here, LNP2141) at 1 mg/kg (BIW, 5total dosings): MYC-1711-M12-M48, MYC-1711-M32-M48, MYC-1711-M50-M73 andMYC-1711-M50-M48. Forty-eight hours after the final dose, mice weresacrificed and tumors were weighed. As shown in FIG. 13, Hep3B tumorgrowth was significantly inhibited by all 2′-O-methyl modified MYC-1711DsiRNAs examined.

The impact upon anti-tumor efficacy of altering the size and frequencyof modified MYC-targeting duplexes was examined. Mice bearing Hep3Borthotopic liver tumors were dosed intravenously with PBS, or withHPRT1-716-M21/M36 or MYC-1711-M50/M48 DsiRNAs formulated in lipidnanoparticle (LNP2141) at doses of 1, 3 or 5 mg/kg (3 mg/kg and 5 mg/kgformulations were dosed either twice-a-week (BIW, 5 total dosings) oronce-a-week (QW, three total dosings), while the 1 mg/kg formulationswere only dosed twice-a-week (BIW)). Forty-eight hours after the finaldose, mice were sacrificed and tumors were weighed. As shown in FIG. 14,tumor growth was significantly inhibited by MYC-1711 DsiRNA at all doses(**, P<0.01; ***, P<0.001; ****, P<0.0001), but not by the HPRT1 DsiRNA.Thus, low-dose DsiRNA administrations were highly effective at reducingHep3B tumor size in vivo.

It was also observed that administration of MYC-targeting DsiRNAs toHep3B tumor bearing mice induced greater reduction of tumor burden thanwas observed for sorafenib when either agent was administeredindividually, and that MYC-targeting DsiRNAs were effective inhibitorsof tumor burden when both sorafenib and MYC-targeting DsiRNAs wereadministered in the Hep3B tumor model—indeed such a combination waswell-tolerated, with no significant weight loss or reduction in spleenor liver weights observed in such combination therapy-treated mice (datanot shown). Administration of MYC-targeting DsiRNAs to Hep3B tumorbearing mice was also confirmed to reduce both MYC transcript andprotein levels in such tumors in dose-dependent fashion, as well aslevels of LDHA protein (LDHA is downstream of MYC in the MYC signalingpathway). MYC DsiRNAs were also confirmed to have low immunostimulatorypotential, as identified in assays for PEG IgM induction, where allMYC-targeting DsiRNAs formulated in LNP formulation EnCore 2072 did notinduce PEG IgM to any greater extent than PBS-treated animals, whileeven when formulated in an LNP designed to be immunostimulatory, mostMYC-targeting DsiRNAs showed no induction of PEG IgM as compared tomock-treated animals (data not shown). IC50 values were also calculatedfor MYC-targeting DsiRNAs and were observed to be in the range of 5-50pM in both Hep3B and Hepa1-6 cells.

The ability of MYC-targeting duplexes to reduce the growth of certainnon-liver tumors was also examined. In one such experiment, mice bearingsubcutaneous HT-29 tumors were dosed intravenously with PBS, or withHPRT1-716-M21/M36 or MYC-621-M12/M12 DsiRNAs formulated in lipidnanoparticle (for these experiments, LNP2163), at 10 mg/kg once a week,for two total DsiRNA dosings. Tumor size was measured during and at theend of the treatment period. As shown in FIG. 15, HT-29 (colon cancermodel) tumor growth was significantly inhibited by MYC-621 DsiRNA (*,P<0.05), but not by the HPRT1 DsiRNA. In another such experiment, micebearing subcutaneous MIA PaCa-2 (pancreatic cancer) tumors were dosedintravenously with PBS, or with HPRT1-716-M21/M36 or MYC-621-M12/M12DsiRNAs in lipid nanoparticle (LNP2163; at 10 mg/kg once a week forthree total dosings). Tumor size was measured during and at the end ofthe treatment period. As shown in FIG. 16, tumor growth wassignificantly inhibited by MYC-621 DsiRNA (***, P<0.001).

Thus, potent DsiRNAs against MYC were identified, with such DsiRNAspossessing picomolar mRNA knockdown activity when transfected into Hep3Bcells. Meanwhile, many such DsiRNAs when modified with 2′-O-methylgroups were observed to have low immunostimulatory potential in vivo.Further, LNP-formulated MYC-targeting DsiRNAs were found to beefficacious in in vivo models of human hepatocellular carcinoma (here,Hep3B and HepG2 tumor models), where MYC-targeting DsiRNAs wereidentified to produce significant tumor reduction of establishedorthotopic HepG2 and Hep3B tumors. It was also confirmed that knockdownof tumor-derived MYC mRNA was sufficient for antitumor activity, andthat such activity was dose-dependent and observed with multipledistinct DsiRNAs, in multiple different types of tumors. In addition,reduced MYC mRNA, Myc protein and downstream LDHA protein levelscorrelated with such anti-tumor activity. Such treatment was alsoobserved to be well-tolerated in combination with sorafenib.Accordingly, MYC-targeting DsiRNAs exhibited potent in vitro and in vivoMYC mRNA knockdown activity and demonstrated significant anti-tumoractivity in the HepG2, Hep3B, HT-29 and MIA PaCa2 orthotopic tumormodels. Such results provide a rationale for the clinical evaluation ofDsiRNA molecules against MYC, a traditionally “undruggable” target, inpatients with advanced HCC.

Example 9 Indications

The present body of knowledge in MYC research indicates the need formethods to assay MYC activity and for compounds that can regulate MYCexpression for research, diagnostic, and therapeutic use. As describedherein, the nucleic acid molecules of the present invention can be usedin assays to diagnose disease state related to MYC levels. In addition,the nucleic acid molecules can be used to treat disease state related toMYC misregulation, levels, etc.

Particular disorders and disease states that can be associated with MYCexpression modulation include, but are not limited to cancer and/orproliferative diseases, conditions, or disorders and other diseases,conditions or disorders that are related to or will respond to thelevels of MYC in a cell or tissue, alone or in combination with othertherapies, such as other immune cell-related disorders (e.g.inflammatory or autoimmune disorders). Particular degenerative anddisease states that are associated with MYC expression modulationinclude but are not limited to, for example, renal, breast, lung, liver,ovarian, cervical, esophageal, oropharyngeal and pancreatic cancer.

Gemcitabine and cyclophosphamide are non-limiting examples ofchemotherapeutic agents that can be combined with or used in conjunctionwith the nucleic acid molecules (e.g. DsiRNA molecules) of the instantinvention. Those skilled in the art will recognize that other drugs suchas anti-cancer compounds and therapies can be similarly be readilycombined with the nucleic acid molecules of the instant invention (e.g.DsiRNA molecules) and are hence within the scope of the instantinvention. Such compounds and therapies are well known in the art (seefor example Cancer: Principles and Practice of Oncology, Volumes 1 and2, eds Devita, V. T., Hellman, S., and Rosenberg, S. A., J. B.Lippincott Company, Philadelphia, USA) and include, without limitations,antifolates; fluoropyrimidines; cytarabine; purine analogs; adenosineanalogs; amsacrine; topoisomerase I inhibitors; anthrapyrazoles;retinoids; antibiotics such as bleomycin, anthacyclins, mitomycin C,dactinomycin, and mithramycin; hexamethylmelamine; dacarbazine;1-asperginase; platinum analogs; alkylating agents such as nitrogenmustard, melphalan, chlorambucil, busulfan, ifosfamide,4-hydroperoxycyclophosphamide, nitrosoureas, thiotepa; plant derivedcompounds such as vinca alkaloids, epipodophyllotoxins, taxol;Tamoxifen; radiation therapy; surgery; nutritional supplements; genetherapy; radiotherapy such as 3D-CRT; immunotoxin therapy such as ricin,monoclonal antibodies such as Herceptin; other therapeutics such astarceva, sorafenib, obatoclax, apogossypolone, and navitoclax, and thelike. For combination therapy, the nucleic acids of the invention areprepared in one of two ways. First, the agents are physically combinedin a preparation of nucleic acid and chemotherapeutic agent, such as amixture of a nucleic acid of the invention encapsulated in liposomes andifosfamide in a solution for intravenous administration, wherein bothagents are present in a therapeutically effective concentration (e.g.,ifosfamide in solution to deliver 1000-1250 mg/m2/day andliposome-associated nucleic acid of the invention in the same solutionto deliver 0.1-100 mg/kg/day). Alternatively, the agents areadministered separately but simultaneously or successively in theirrespective effective doses (e.g., 1000-1250 mg/m2/d ifosfamide and 0.1to 100 mg/kg/day nucleic acid of the invention).

Those skilled in the art will recognize that other compounds andtherapies used to treat the diseases and conditions described herein cansimilarly be combined with the nucleic acid molecules of the instantinvention (e.g. siNA molecules) and are hence within the scope of theinstant invention.

Example 10 Serum Stability for DsiRNAs

Serum stability of DsiRNA agents is assessed via incubation of DsiRNAagents in 50% fetal bovine serum for various periods of time (up to 24h) at 37° C. Serum is extracted and the nucleic acids are separated on a20% non-denaturing PAGE and can be visualized with Gelstar stain.Relative levels of protection from nuclease degradation are assessed forDsiRNAs (optionally with and without modifications).

Example 11 Use of Additional Cell Culture Models to Evaluate theDown-Regulation of MYC Gene Expression

A variety of endpoints have been used in cell culture models to look atMYC-mediated effects after treatment with anti-MYC agents. Phenotypicendpoints include inhibition of cell proliferation, RNA expression, andreduction of Myc protein expression. Because MYC mutations are directlyassociated with increased growth of certain tumor cells, a growthendpoint for cell culture assays can be used as a screen. There areseveral methods by which this endpoint can be measured. Followingtreatment of cells with DsiRNA, cells are allowed to grow (typically 5days), after which the cell viability, the incorporation ofbromodeoxyuridine (BrdU) into cellular DNA and/or the cell density aremeasured. The assay of cell density can be done in a 96-well formatusing commercially available fluorescent nucleic acid stains (such asSyto® 13 or CyQuant®). As a secondary, confirmatory endpoint, aDsiRNA-mediated decrease in the level of Myc protein expression can beevaluated using a MYC-specific Western assay. The following areexemplary cell lines for use in such assays (e.g., assays performed asdescribed in Schulze-Bergkamen et al., BMC Cancer 2006, 6:232, fordetection of Mc1-1 expression): A549, H1299, HepG2, SNU398, A549,NCI-H196, NCI-H1975, MDA-MB-231, NCI-H441, Panc-1, MIA PaCa, BxPC3,DU-145, VCaP, MCF-7, U937, K562, HeLa, or T98G cells.

Example 12 Evaluation of Anti-MYC DsiRNA Efficacy in Additional MouseModels of MYC Misregulation

Anti-MYC DsiRNA chosen from in vitro assays can be further tested inmouse models, including, e.g., xenograft and other animal models asrecited above. As referred to above, exemplary appropriate cell linesfor use in xenograft assays include HT1080, HCT116, SW480, SW620, Hep3B,M14, JR8, PLF2, LLC1, LNCaP, PC3, SUM159, MDAMB-231, 22Rv1, 518A2,MHCC97, A549, H1299, HepG2, SNU398, HuH7, NCI-H196, NCI-H1975, HT29,MKN-45, MDA-MB-231, NCI-H441, Panc-1, MIA PaCa-2, BxPC3, DU-145, M2182,VCaP, OvCar-3, MCF-7, U937, K562, HeLa, T98G, or SHP-77. In one example,mice possessing misregulated (e.g., elevated) MYC levels areadministered a DsiRNA agent of the present invention via hydrodynamictail vein injection and/or lipid nanoparticle-based delivery modality.3-4 mice per group (divided based upon specific DsiRNA agent tested) areinjected with 50 μg or 200 μg of DsiRNA. Levels of MYC RNA are evaluatedusing RT-qPCR. Additionally or alternatively, levels of MYC (e.g., Mycprotein levels and/or cancer cell/tumor formation, growth or spread) canbe evaluated using an art-recognized method, or phenotypes associatedwith misregulation of MYC (e.g., tumor formation, growth, metastasis,etc.) are monitored (optionally as a proxy for measurement of MYCtranscript or Myc protein levels). Active DsiRNA in such animal modelscan also be subsequently tested in combination with standardchemotherapies.

Example 13 Diagnostic Uses

The DsiRNA molecules of the invention can be used in a variety ofdiagnostic applications, such as in the identification of moleculartargets (e.g., RNA) in a variety of applications, for example, inclinical, industrial, environmental, agricultural and/or researchsettings. Such diagnostic use of DsiRNA molecules involves utilizingreconstituted RNAi systems, for example, using cellular lysates orpartially purified cellular lysates. DsiRNA molecules of this inventioncan be used as diagnostic tools to examine genetic drift and mutationswithin diseased cells. The close relationship between DsiRNA activityand the structure of the target MYC RNA allows the detection ofmutations in a region of the MYC molecule, which alters the base-pairingand three-dimensional structure of the target MYC RNA. By using multipleDsiRNA molecules described in this invention, one can map nucleotidechanges, which are important to RNA structure and function in vitro, aswell as in cells and tissues. Cleavage of target MYC RNAs with DsiRNAmolecules can be used to inhibit gene expression and define the role ofspecified gene products in the progression of a MYC-associated diseaseor disorder. In this manner, other genetic targets can be defined asimportant mediators of the disease. These experiments will lead tobetter treatment of the disease progression by affording the possibilityof combination therapies (e.g., multiple DsiRNA molecules targeted todifferent genes, DsiRNA molecules coupled with known small moleculeinhibitors, or intermittent treatment with combinations of DsiRNAmolecules and/or other chemical or biological molecules). Other in vitrouses of DsiRNA molecules of this invention are well known in the art,and include detection of the presence of RNAs associated with a diseaseor related condition. Such RNA is detected by determining the presenceof a cleavage product after treatment with a DsiRNA using standardmethodologies, for example, fluorescence resonance emission transfer(FRET).

In a specific example, DsiRNA molecules that cleave only wild-type ormutant or polymorphic forms of the target MYC RNA are used for theassay. The first DsiRNA molecules (i.e., those that cleave onlywild-type forms of target MYC RNA) are used to identify wild-type MYCRNA present in the sample and the second DsiRNA molecules (i.e., thosethat cleave only mutant or polymorphic forms of target RNA) are used toidentify mutant or polymorphic MYC RNA in the sample. As reactioncontrols, synthetic substrates of both wild-type and mutant orpolymorphic MYC RNA are cleaved by both DsiRNA molecules to demonstratethe relative DsiRNA efficiencies in the reactions and the absence ofcleavage of the “non-targeted” MYC RNA species. The cleavage productsfrom the synthetic substrates also serve to generate size markers forthe analysis of wild-type and mutant MYC RNAs in the sample population.Thus, each analysis requires two DsiRNA molecules, two substrates andone unknown sample, which is combined into six reactions. The presenceof cleavage products is determined using an RNase protection assay sothat full-length and cleavage fragments of each MYC RNA can be analyzedin one lane of a polyacrylamide gel. It is not absolutely required toquantify the results to gain insight into the expression of mutant orpolymorphic MYC RNAs and putative risk of MYC-associated phenotypicchanges in target cells. The expression of MYC mRNA whose proteinproduct is implicated in the development of the phenotype (i.e., diseaserelated/associated) is adequate to establish risk. If probes ofcomparable specific activity are used for both transcripts, then aqualitative comparison of MYC RNA levels is adequate and decreases thecost of the initial diagnosis. Higher mutant or polymorphic form towild-type ratios are correlated with higher risk whether MYC RNA levelsare compared qualitatively or quantitatively.

All patents and publications mentioned in the specification areindicative of the levels of skill of those skilled in the art to whichthe invention pertains. All references cited in this disclosure areincorporated by reference to the same extent as if each reference hadbeen incorporated by reference in its entirety individually.

One skilled in the art would readily appreciate that the presentinvention is well adapted to carry out the objects and obtain the endsand advantages mentioned, as well as those inherent therein. The methodsand compositions described herein as presently representative ofpreferred embodiments are exemplary and are not intended as limitationson the scope of the invention. Changes therein and other uses will occurto those skilled in the art, which are encompassed within the spirit ofthe invention, are defined by the scope of the claims.

It will be readily apparent to one skilled in the art that varyingsubstitutions and modifications can be made to the invention disclosedherein without departing from the scope and spirit of the invention.Thus, such additional embodiments are within the scope of the presentinvention and the following claims. The present invention teaches oneskilled in the art to test various combinations and/or substitutions ofchemical modifications described herein toward generating nucleic acidconstructs with improved activity for mediating RNAi activity. Suchimproved activity can comprise improved stability, improvedbioavailability, and/or improved activation of cellular responsesmediating RNAi. Therefore, the specific embodiments described herein arenot limiting and one skilled in the art can readily appreciate thatspecific combinations of the modifications described herein can betested without undue experimentation toward identifying DsiRNA moleculeswith improved RNAi activity.

The invention illustratively described herein suitably can be practicedin the absence of any element or elements, limitation or limitationsthat are not specifically disclosed herein. Thus, for example, in eachinstance herein any of the terms “comprising”, “consisting essentiallyof”, and “consisting of” may be replaced with either of the other twoterms. The terms and expressions which have been employed are used asterms of description and not of limitation, and there is no intentionthat in the use of such terms and expressions of excluding anyequivalents of the features shown and described or portions thereof, butit is recognized that various modifications are possible within thescope of the invention claimed. Thus, it should be understood thatalthough the present invention has been specifically disclosed bypreferred embodiments, optional features, modification and variation ofthe concepts herein disclosed may be resorted to by those skilled in theart, and that such modifications and variations are considered to bewithin the scope of this invention as defined by the description and theappended claims.

In addition, where features or aspects of the invention are described interms of Markush groups or other grouping of alternatives, those skilledin the art will recognize that the invention is also thereby describedin terms of any individual member or subgroup of members of the Markushgroup or other group.

The use of the terms “a” and “an” and “the” and similar referents in thecontext of describing the invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. The terms “comprising,” “having,” “including,” and “containing”are to be construed as open-ended terms (i.e., meaning “including, butnot limited to,”) unless otherwise noted. Recitation of ranges of valuesherein are merely intended to serve as a shorthand method of referringindividually to each separate value falling within the range, unlessotherwise indicated herein, and each separate value is incorporated intothe specification as if it were individually recited herein. All methodsdescribed herein can be performed in any suitable order unless otherwiseindicated herein or otherwise clearly contradicted by context. The useof any and all examples, or exemplary language (e.g., “such as”)provided herein, is intended merely to better illuminate the inventionand does not pose a limitation on the scope of the invention unlessotherwise claimed. No language in the specification should be construedas indicating any non-claimed element as essential to the practice ofthe invention.

Embodiments of this invention are described herein, including the bestmode known to the inventors for carrying out the invention. Variationsof those embodiments may become apparent to those of ordinary skill inthe art upon reading the foregoing description.

The inventors expect skilled artisans to employ such variations asappropriate, and the inventors intend for the invention to be practicedotherwise than as specifically described herein. Accordingly, thisinvention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, many equivalents to the specificembodiments of the invention described herein. Such equivalents areintended to be encompassed by the following claims.

We claim:
 1. An isolated nucleic acid comprising an oligonucleotide strand of 15-50 nucleotides in length, wherein said oligonucleotide strand is complementary to 5′-CAAGGUAGUUAUCCUUAAAAAAGCCAC-3′ (SEQ ID NO: 2028) along at least 15 consecutive nucleotides of said oligonucleotide strand length and reduces MYC target mRNA expression when said nucleic acid is introduced into a mammalian cell.
 2. An isolated nucleic acid comprising an oligonucleotide strand of 19-50 nucleotides in length, wherein said oligonucleotide strand is complementary to 5′-CAAGGUAGUUAUCCUUAAAAAAGCCAC-3′ (SEQ ID NO: 2028) along at least 19 consecutive nucleotides of said oligonucleotide strand length and reduces MYC target mRNA expression when said nucleic acid is introduced into a mammalian cell.
 3. An isolated double stranded nucleic acid (dsNA) comprising first and second nucleic acid strands, wherein said first strand is 15-50 nucleotides in length and said second strand of said dsNA is 19-50 nucleotides in length, wherein said second strand is complementary to 5′-CAAGGUAGUUAUCCUUAAAAAAGCCAC-3′ (SEQ ID NO: 2028) along at least 15 consecutive nucleotides of said second strand length and said dsNA reduces MYC target mRNA expression when said dsNA is introduced into a mammalian cell.
 4. An isolated double stranded nucleic acid (dsNA) comprising first and second nucleic acid strands, wherein said first strand is 15-50 nucleotides in length and said second strand of said dsNA is 19-50 nucleotides in length, wherein said second strand is complementary to 5′-CAAGGUAGUUAUCCUUAAAAAAGCCAC-3′ (SEQ ID NO: 2028) along at least 19 consecutive nucleotides of said second strand length and said dsNA reduces MYC target mRNA expression when said dsNA is introduced into a mammalian cell.
 5. An isolated double stranded nucleic acid (dsNA) comprising first and second nucleic acid strands and a duplex region of at least 25 base pairs, wherein said first strand is 25-34 nucleotides in length and said second strand of said dsNA is 26-50 nucleotides in length and comprises 1-5 single-stranded nucleotides at its 3′ terminus, wherein said second strand is complementary to 5′-CAAGGUAGUUAUCCUUAAAAAAGCCAC-3′ (SEQ ID NO: 2028) along at least 19 consecutive nucleotides of said second strand length and said dsNA reduces MYC target gene expression when said dsNA is introduced into a mammalian cell.
 6. An isolated double stranded nucleic acid (dsNA) comprising first and second nucleic acid strands and a duplex region of at least 25 base pairs, wherein said first strand is 25-34 nucleotides in length and said second strand of said dsNA is 26-35 nucleotides in length and comprises 1-5 single-stranded nucleotides at its 3′ terminus, wherein the 3′ terminus of said first strand and the 5′ terminus of said second strand form a blunt end, and said second strand is complementary to 5′-CAAGGUAGUUAUCCUUAAAAAAGCCAC-3′ (SEQ ID NO: 2028) along at least 19 consecutive nucleotides of said second strand length and said dsNA reduces MYC mRNA expression when said dsNA is introduced into a mammalian cell.
 7. The isolated dsNA of claim 3 comprising a duplex region selected from the group consisting of at least 25 base pairs; 19-21 base pairs and 21-25 base pairs.
 8. The isolated dsNA of claim 3, wherein said second oligonucleotide strand comprises 1-5 single-stranded nucleotides at its 3′ terminus.
 9. The isolated dsNA of claim 3, wherein said first strand is 25-35 nucleotides in length.
 10. The isolated dsNA of claim 3, wherein said second strand is 25-35 nucleotides in length.
 11. The isolated dsNA of claim 3, wherein starting from the first nucleotide (position 1) at the 3′ terminus of the first oligonucleotide strand, position 1, 2 and/or 3 is substituted with a modified nucleotide.
 12. The isolated dsNA of claim 3, wherein said 3′ terminus of said first strand and said 5′ terminus of said second strand form a blunt end.
 13. The isolated dsNA of claim 3, wherein said first strand is 25 nucleotides in length and said second strand is 27 nucleotides in length.
 14. The isolated dsNA of claim 3, wherein said second strand comprises 5′-GUGGCUUUUUUAAGGAUAACUACCUUG-3′ (SEQ ID NO: 393).
 15. The isolated dsNA of claim 3, wherein said first strand comprises a sequence selected from the group consisting of SEQ ID NOs: 66, 1047, 1374, 2028, 2355, 2682, and
 3009. 16. The isolated dsNA of claim 3 comprising SEQ ID NOs: 66 and
 393. 17. The isolated dsNA of claim 11, wherein said modified nucleotide residue of said 3′ terminus of said first strand is selected from the group consisting of a deoxyribonucleotide, an acyclonucleotide and a fluorescent molecule.
 18. The isolated dsNA of claim 17, wherein position 1 of said 3′ terminus of the first strand is a deoxyribonucleotide.
 19. The isolated dsNA of claim 5, wherein said nucleotides of said 1-5 single-stranded nucleotides of said 3′ terminus of said second strand comprise a modified nucleotide.
 20. The isolated dsNA of claim 19, wherein said modified nucleotide of said 1-5 single-stranded nucleotides of said 3′ terminus of said second strand is a 2′-O-methyl ribonucleotide.
 21. The isolated dsNA of claim 19, wherein all nucleotides of said 1-5 single-stranded nucleotides of said 3′ terminus of said second strand are modified nucleotides.
 22. The isolated dsNA of claim 3, wherein said dsNA comprises a modified nucleotide.
 23. The isolated dsNA of claim 22, wherein said modified nucleotide residue is selected from the group consisting of 2′-O-methyl, 2′-methoxyethoxy, 2′-fluoro, 2′-allyl, 2′-O[2-(methylamino)-2-oxoethyll, 4′-thio, 4′-CH2-O-2′-bridge, 4′-(CH2)2-O-2′-bridge, 2′-LNA, 2′-amino and 2′-O-(N-methlycarbamate).
 24. The isolated dsNA of claim 5, wherein said 1-5 single-stranded nucleotides of said 3′ terminus of said second strand are 1-3 nucleotides in length.
 25. The isolated dsNA of claim 5, wherein said 1-5 single-stranded nucleotides of said 3′ terminus of said second strand are 1-2 nucleotides in length.
 26. The isolated dsNA of claim 5, wherein said 1-5 single-stranded nucleotides of said 3′ terminus of said second strand is two nucleotides in length and comprises a 2′-O-methyl modified ribonucleotide.
 27. The isolated dsNA of claim 3, wherein said second oligonucleotide strand comprises an AS-M48 modification pattern.
 28. The isolated dsNA of claim 3, wherein said first oligonucleotide strand comprises an S-M12 modification pattern.
 29. The isolated dsNA of claim 3, wherein said dsNA is cleaved endogenously in said cell by Dicer.
 30. The isolated dsNA of claim 3, wherein the amount of said isolated nucleic acid sufficient to reduce expression of the target gene is selected from the group consisting of 1 nanomolar or less, 200 picomolar or less, 100 picomolar or less, 50 picomolar or less, 20 picomolar or less, 10 picomolar or less, 5 picomolar or less, 2, picomolar or less and 1 picomolar or less in the environment of said cell.
 31. The isolated dsNA of claim 3, wherein said isolated dsNA reduces MYC target mRNA expression by an amount (expressed by %) selected from the group consisting of at least 10%, at least 50%, at least 80-90%, at least 95%, at least 98%, and at least 99% when said double stranded nucleic acid is introduced into a mammalian cell.
 32. The isolated dsNA of claim 3, wherein the first and second strands are joined by a chemical linker.
 33. The isolated double stranded nucleic acid of claim 3, wherein said 3′ terminus of said first strand and said 5′ terminus of said second strand are joined by a chemical linker.
 34. The isolated double stranded nucleic acid of claim 3, wherein a nucleotide of said second or first strand is substituted with a modified nucleotide that directs the orientation of Dicer cleavage.
 35. The isolated nucleic acid of claim 1 comprising a modified nucleotide selected from the group consisting of a deoxyribonucleotide, a dideoxyribonucleotide, an acyclonucleotide, a 3′-deoxyadenosine (cordycepin), a 3′-azido-3′-deoxythymidine (AZT), a 2′,3′-dideoxyinosine (ddI), a 2′,3′-dideoxy-3′-thiacytidine (3TC), a 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T), a monophosphate nucleotide of 3′-azido-3′-deoxythymidine (AZT), a 2′,3′-dideoxy-3′-thiacytidine (3TC) and a monophosphate nucleotide of 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T), a 4-thiouracil, a 5-bromouracil, a 5-iodouracil, a 5-(3-aminoallyl)-uracil, a 2′-0-alkyl ribonucleotide, a 2′-0-methyl ribonucleotide, a 2′-amino ribonucleotide, a 2′-fluoro ribonucleotide, and a locked nucleic acid.
 36. The isolated nucleic acid of claim 1 comprising a phosphate backbone modification selected from the group consisting of a phosphonate, a phosphorothioate and a phosphotriester.
 37. The isolated nucleic acid of claim 1 comprising a modification selected from the group consisting of a morpholino nucleic acid and a peptide nucleic acid (PNA).
 38. A method for reducing expression of a target MYC gene in a mammalian cell comprising contacting a mammalian cell in vitro with an isolated dsNA of claim 3 in an amount sufficient to reduce expression of a target MYC mRNA in said cell.
 39. The method of claim 38, wherein target MYC mRNA expression is reduced by an amount (expressed by %) selected from the group consisting of at least 10%, at least 50% and at least 80-90%.
 40. The method of claim 38, wherein MYC mRNA levels are reduced by an amount (expressed by %) of at least 90% at least 8 days after said cell is contacted with said dsNA.
 41. The method of claim 38, wherein MYC mRNA levels are reduced by an amount (expressed by %) of at least 70% at least 10 days after said cell is contacted with said dsNA.
 42. A method for reducing expression of a target MYC mRNA in a mammal comprising administering an isolated nucleic acid of claim 1 to a mammal in an amount sufficient to reduce expression of a target MYC mRNA in the mammal.
 43. A method for reducing tumor burden in a mammal comprising administering an isolated nucleic acid of claim 1 to a mammal in an amount sufficient to reduce tumor burden in said mammal.
 44. The method of claim 43, wherein said tumor is a hepatocellular carcinoma.
 45. The method of claim 43, wherein said tumor burden is reduced by 50-80%, as compared to a suitable control.
 46. The method of claim 43, wherein said isolated nucleic acid is formulated in a lipid nanoparticle (LNP).
 47. The method of claim 42, wherein said isolated nucleic acid is administered at a dosage selected from the group consisting of 1 microgram to 5 milligrams per kilogram of said mammal per day, 100 micrograms to 0.5 milligrams per kilogram, 0.001 to 0.25 milligrams per kilogram, 0.01 to 20 micrograms per kilogram, 0.01 to 10 micrograms per kilogram, 0.10 to 5 micrograms per kilogram, and 0.1 to 2.5 micrograms per kilogram.
 48. The method of claim 42, wherein MYC mRNA levels are reduced in a tissue of said mammal by an amount (expressed by %) of at least 70% at least 3 days after said isolated dsNA is administered to said mammal.
 49. The method claim 48, wherein said tissue is liver tissue.
 50. The method of claim 42, wherein said administering step comprises a mode selected from the group consisting of intravenous injection, intramuscular injection, intraperitoneal injection, infusion, subcutaneous injection, transdermal, aerosol, rectal, vaginal, topical, oral and inhaled delivery.
 51. A method for selectively inhibiting the growth of a cell comprising contacting a cell with an amount of an isolated nucleic acid of claim 1 sufficient to inhibit the growth of the cell.
 52. The method of claim 51, wherein said cell is a tumor cell of a subject.
 53. The method of claim 51, wherein said cell is a tumor cell in vitro.
 54. The method of claim 51, wherein said cell is a human cell.
 55. A formulation comprising the isolated nucleic acid of claim 1, wherein said nucleic acid is present in an amount effective to reduce target MYC mRNA levels when said nucleic acid is introduced into a mammalian cell in vitro by an amount (expressed by %) selected from the group consisting of at least 10%, at least 50% and at least 80-90%.
 56. A formulation comprising the isolated dsNA of claim 3, wherein said dsNA is present in an amount effective to reduce target MYC mRNA levels when said dsNA is introduced into a cell of a mammalian subject by an amount (expressed by %) selected from the group consisting of at least 10%, at least 50% and at least 80-90%.
 57. An isolated mammalian cell containing the nucleic acid of claim
 1. 58. A pharmaceutical composition comprising the isolated nucleic acid of claim 1 and a pharmaceutically acceptable carrier.
 59. A kit comprising the isolated nucleic acid of claim 1 and instructions for its use.
 60. A method for treating or preventing a MYC-associated disease or disorder in a subject comprising administering the isolated nucleic acid of claim 1 and a pharmaceutically acceptable carrier to the subject in an amount sufficient to treat or prevent said MYC-associated disease or disorder in said subject, thereby treating or preventing said MYC-associated disease or disorder in said subject.
 61. The method of claim 60, wherein said MYC-associated disease or disorder is selected from the group consisting of liver, renal, breast, lung, ovarian, cervical, esophageal, oropharyngeal and pancreatic cancer.
 62. The method of claim 61, wherein said MYC-associated disease or disorder is hepatocellular carcinoma.
 63. A composition possessing MYC inhibitory activity consisting essentially of an isolated nucleic acid of claim
 1. 64. The isolated double stranded nucleic acid of claim 3, wherein said second strand comprises the complement of at least one sequence selected from the group consisting of SEQ ID NOs: 1047, 1374, 2028, 2355, 2682, and
 3009. 